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Włoch A, Sengupta P, Szulc N, Kral T, Pawlak A, Henklewska M, Pruchnik H, Sykora J, Hof M, Gładkowski W. Biophysical and molecular interactions of enantiomeric piperonal-derived trans β-aryl-δ-iodo-γ-lactones with cancer cell membranes, protein and DNA: Implications for anticancer activity. Int J Biol Macromol 2025; 303:140476. [PMID: 39900147 DOI: 10.1016/j.ijbiomac.2025.140476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Revised: 01/21/2025] [Accepted: 01/27/2025] [Indexed: 02/05/2025]
Abstract
Developing novel anticancer agents requires understanding their interactions with biological systems at both the cellular and molecular levels. Enantiomeric lactones have demonstrated notable cytotoxic activities against various cancer cell lines. Building on this foundation, we investigated enantiomeric piperonal-derived trans-β-aryl-δ-iodo-γ-lactones ((-)-(4S,5R,6S) and (+)-(4R,5S,6R)), focusing on their impact on cancer cells membrane (Jurkat and GL-1), model membranes, and biomacromolecules such as human serum albumin (HSA) and DNA. Also, the cytotoxicity toward red blood cells and the antitumor activity of the compounds were evaluated against a set of canine lymphoma and/or leukemia cell lines. Membrane interaction studies revealed that both enantiomers interact with the hydrophobic core of lipid bilayers, enhancing lipid acyl chain packing, with the (-)-(4S,5R,6S) isomer showing a stronger impact on membrane fluidity. Comprehensive spectroscopic and theoretical studies revealed distinct stereochemical differences in binding affinities to HSA, where the (-)-(4S,5R,6S) isomer showed higher binding affinity and significant hydrophobic interactions. Detailed biological studies demonstrated that both enantiomers exhibit antiproliferative and proapoptotic activities, with the (-)-(4S,5R,6S) enantiomer showing higher activity. This study underscores the biological activity and interactions of enantiomeric iodolactones derived from piperonal with biomacromolecules, providing comprehensive insights into their biophysical behavior and potential anticancer properties.
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Affiliation(s)
- Aleksandra Włoch
- Department of Physics and Biophysics, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, Poland.
| | - Priti Sengupta
- Department of Physics and Biophysics, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, Poland
| | - Natalia Szulc
- Department of Physics and Biophysics, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, Poland
| | - Teresa Kral
- Department of Physics and Biophysics, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, Poland; Department of Biophysical Chemistry, J. Heyrovsky Institute of Physical Chemistry of the Czech Academy of Sciences, Dolejskova 3, 18223 Prague, Czech Republic
| | - Aleksandra Pawlak
- Department of Pharmacology and Toxicology, Wrocław University of Environmental and Life Sciences, Norwida 31, 50-375 Wrocław, Poland
| | - Marta Henklewska
- Department of Pharmacology and Toxicology, Wrocław University of Environmental and Life Sciences, Norwida 31, 50-375 Wrocław, Poland
| | - Hanna Pruchnik
- Department of Physics and Biophysics, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, Poland
| | - Jan Sykora
- Department of Biophysical Chemistry, J. Heyrovsky Institute of Physical Chemistry of the Czech Academy of Sciences, Dolejskova 3, 18223 Prague, Czech Republic
| | - Martin Hof
- Department of Biophysical Chemistry, J. Heyrovsky Institute of Physical Chemistry of the Czech Academy of Sciences, Dolejskova 3, 18223 Prague, Czech Republic
| | - Witold Gładkowski
- Department of Food Chemistry and Biocatalysis, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, Poland
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Devinat M, Thevenard-Devy J, Ghilane F, Devy J, Chazee L, Terryn C, Duca L, Devarenne-Charpentier E, El Btaouri H. Xanthohumol Sensitizes Melanoma Cells to Vemurafenib by Lowering Membrane Cholesterol and Increasing Membrane Fluidity. Int J Mol Sci 2025; 26:2290. [PMID: 40076912 PMCID: PMC11901044 DOI: 10.3390/ijms26052290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2025] [Revised: 02/26/2025] [Accepted: 02/28/2025] [Indexed: 03/14/2025] Open
Abstract
Chemoresistance remains one of the major obstacles to cancer treatment. The search for specific molecules that could improve cancer treatment has become one of the objectives of biomedical research. Identifying new natural molecules to enhance chemotherapy treatment or improve sensitization to conventional therapies has become a key objective. Here, we evaluated the effect of Xanthohumol (XN) extracted from hop on SKMEL-28 melanoma cells and their sensitization to vemurafenib (VEM) treatment. We measured the XN effect on cell viability and apoptosis. We also assessed the effect of XN on membrane fluidity and membrane cholesterol levels. Finally, we studied the impact of XN on cell sensitization to VEM. Here, we showed that XN reduced SKMEL-28 cell viability through an apoptotic mechanism. Our results demonstrated the potential role of XN in sensitizing cancer cells to VEM with a less toxic effect on non-tumor cells. A study of XN's molecular mechanism showed that XN was able to induce cholesterol depletion and increased fluidity in SKMEL-28 cancer cells. This leads to an increase in VEM incorporation. Here, we describe the importance of the strategy to modulate membrane fluidity by XN in order to significantly improve anticancer therapy.
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Affiliation(s)
- Marine Devinat
- UMR-CNRS 7369 Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), UFR Sciences Exactes et Naturelles, Université de Reims Champagne Ardenne, Moulin de la Housse, BP 1039, 51687 Reims, CEDEX, France; (M.D.); (J.T.-D.); (J.D.); (L.C.); (L.D.); (E.D.-C.)
| | - Jessica Thevenard-Devy
- UMR-CNRS 7369 Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), UFR Sciences Exactes et Naturelles, Université de Reims Champagne Ardenne, Moulin de la Housse, BP 1039, 51687 Reims, CEDEX, France; (M.D.); (J.T.-D.); (J.D.); (L.C.); (L.D.); (E.D.-C.)
| | - Fatiha Ghilane
- Laboratoire de Biologie des Pathologies Humaines, Université Mohammed V de Rabat, 4 Avenue Ibn Battouta, Rabat B.P. 1014 RP, Morocco;
| | - Jerome Devy
- UMR-CNRS 7369 Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), UFR Sciences Exactes et Naturelles, Université de Reims Champagne Ardenne, Moulin de la Housse, BP 1039, 51687 Reims, CEDEX, France; (M.D.); (J.T.-D.); (J.D.); (L.C.); (L.D.); (E.D.-C.)
| | - Lise Chazee
- UMR-CNRS 7369 Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), UFR Sciences Exactes et Naturelles, Université de Reims Champagne Ardenne, Moulin de la Housse, BP 1039, 51687 Reims, CEDEX, France; (M.D.); (J.T.-D.); (J.D.); (L.C.); (L.D.); (E.D.-C.)
| | - Christine Terryn
- Plateau Technique en Imagerie Cellulaire et Tissulaire (PICT) Pôle Santé, UFR Pharmacie, Université de Reims Champagne Ardenne, 51 Rue Cognacq Jay, 51096 Reims, France;
| | - Laurent Duca
- UMR-CNRS 7369 Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), UFR Sciences Exactes et Naturelles, Université de Reims Champagne Ardenne, Moulin de la Housse, BP 1039, 51687 Reims, CEDEX, France; (M.D.); (J.T.-D.); (J.D.); (L.C.); (L.D.); (E.D.-C.)
| | - Emmanuelle Devarenne-Charpentier
- UMR-CNRS 7369 Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), UFR Sciences Exactes et Naturelles, Université de Reims Champagne Ardenne, Moulin de la Housse, BP 1039, 51687 Reims, CEDEX, France; (M.D.); (J.T.-D.); (J.D.); (L.C.); (L.D.); (E.D.-C.)
| | - Hassan El Btaouri
- UMR-CNRS 7369 Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), UFR Sciences Exactes et Naturelles, Université de Reims Champagne Ardenne, Moulin de la Housse, BP 1039, 51687 Reims, CEDEX, France; (M.D.); (J.T.-D.); (J.D.); (L.C.); (L.D.); (E.D.-C.)
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Fuselier C, Dufay E, Berquand A, Terryn C, Bonnomet A, Molinari M, Martiny L, Schneider C. Dynamized ultra-low dilution of Ruta graveolens disrupts plasma membrane organization and decreases migration of melanoma cancer cell. Cell Adh Migr 2023; 17:1-13. [PMID: 36503402 PMCID: PMC9746621 DOI: 10.1080/19336918.2022.2154732] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Accepted: 11/30/2022] [Indexed: 12/14/2022] Open
Abstract
Cutaneous melanoma is a cancer with a very poor prognosis mainly because of metastatic dissemination and therefore a deregulation of cell migration. Current therapies can benefit from complementary medicines as supportive care in oncology. In our study, we show that a dynamized ultra-low dilution of Ruta Graveolens leads to an in vitro inhibition of migration on fibronectin of B16F10 melanoma cells, as well as a decrease in metastatic dissemination in vivo. These effects appear to be due to a disruption of plasma membrane organization, with a change in cell and membrane stiffness, associated with a disorganization of the actin cytoskeleton and a modification of the lipid composition of the plasma membrane. Together, these results demonstrate, in in vitro and in vivo models of cutaneous melanoma, an anti-cancer and anti-metastatic activity of ultra-low dynamized dilution of Ruta graveolens and reinforce its interest as complementary medicine in oncology.
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Affiliation(s)
- Camille Fuselier
- Center Armand-Frappier Santé Biotechnologie of the INRS, University of Quebec, Laval, Quebec, Canada
| | - Eleonore Dufay
- CNRS UMR 7369 MEDyC, University of Reims Champagne-Ardenne, Reims, France
| | | | - Christine Terryn
- Platform PICT, University of Reims Champagne-Ardenne, Reims, France
| | - Arnaud Bonnomet
- Platform PICT, University of Reims Champagne-Ardenne, Reims, France
| | - Michael Molinari
- Institute of Chemistry & Biology of Membranes & Nano-objects, Bordeaux, France
| | - Laurent Martiny
- CNRS UMR 7369 MEDyC, University of Reims Champagne-Ardenne, Reims, France
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Sahin I, Ceylan Ç, Bayraktar O. Ruscogenin interacts with DPPC and DPPG model membranes and increases the membrane fluidity: FTIR and DSC studies. Arch Biochem Biophys 2023; 733:109481. [PMID: 36522815 DOI: 10.1016/j.abb.2022.109481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Revised: 11/14/2022] [Accepted: 11/24/2022] [Indexed: 11/27/2022]
Abstract
Ruscogenin, a kind of steroid saponin, has been shown to have significant anti-oxidant, anti-inflammatory, and anti-thrombotic characteristics. Furthermore, it has the potential to be employed as a medicinal medication to treat a variety of acute and chronic disorders. The interaction of a drug molecule with cell membranes can help to elucidate its system-wide protective and therapeutic effects, and it's also important for its pharmacological activity. The molecular mechanism by which ruscogenin affects membrane architecture is still a mystery. Ruscogenin's interaction with zwitterionic dipalmitoyl phosphatidylcholine (DPPC) and anionic dipalmitoyl phosphatidylglycerol (DPPG) multilamellar vesicles (MLVs) was studied utilizing two non-invasive approaches, including: Fourier Transform Infrared (FTIR) spectroscopy and Differential Scanning Calorimetry. Ruscogenin caused considerable alterations in the phase transition profile, order, dynamics and hydration state of head groups and glycerol backbone of DPPC and DPPG MLVs at all concentrations. The DSC results indicated that the presence of ruscogenin decreased the main phase transition temperature (Tm) and enthalpy (ΔH) values of both membranes and increased half height width of the main transition (ΔT1/2). The FTIR results demonstrated that all concentrations (1, 3, 6, 9, 15, 24 and 30 mol percent) of ruscogenin disordered the DPPC MLVs both in the gel and liquid crystalline phases while it increased the order of DPPG MLVs in the liquid crystalline phase. Moreover, ruscogenin caused an increase in the dynamics of DPPC and DPPG MLVs in both phases. Additionally, it enhanced the hydration of the head groups of lipids and the surrounding water molecules implying ruscogenin to interact strongly with both zwitterionic and charged model membranes.
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Affiliation(s)
- Ipek Sahin
- Department of Physics, Faculty of Science, Ege University, 35100, Bornova, İzmir, Turkey.
| | - Çağatay Ceylan
- Department of Food Engineering, Faculty of Engineering, İzmir Institute of Technology, Urla, İzmir, Turkey
| | - Oguz Bayraktar
- Department of Bioengineering, Faculty of Engineering, Ege University, 35100, Bornova, İzmir, Turkey
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The Advanced Properties of Circularized MSP Nanodiscs Facilitate High-resolution NMR Studies of Membrane Proteins. J Mol Biol 2022; 434:167861. [PMID: 36273602 DOI: 10.1016/j.jmb.2022.167861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 10/12/2022] [Accepted: 10/16/2022] [Indexed: 11/06/2022]
Abstract
Membrane mimetics are essential for structural and functional studies of membrane proteins. A promising lipid-based system are phospholipid nanodiscs, where two copies of a so-called membrane scaffold protein (MSP) wrap around a patch of lipid bilayer. Consequently, the size of a nanodisc is determined by the length of the MSP. Furthermore, covalent MSP circularization was reported to improve nanodisc stability. However, a more detailed comparative analysis of the biophysical properties of circularized and linear MSP nanodiscs for their use in high-resolution NMR has not been conducted so far. Here, we analyze the membrane fluidity and temperature-dependent size variability of circularized and linear nanodiscs using a large set of analytical methods. We show that MSP circularization does not alter the membrane fluidity in nanodiscs. Further, we show that the phase transition temperature increases for circularized versions, while the cooperativity decreases. We demonstrate that circularized nanodiscs keep a constant size over a large temperature range, in contrast to their linear MSP counterparts. Due to this size stability, circularized nanodiscs are beneficial for high-resolution NMR studies of membrane proteins at elevated temperatures. Despite their slightly larger size as compared to linear nanodiscs, 3D NMR experiments of the voltage-dependent anion channel 1 (VDAC1) in circularized nanodiscs have a markedly improved spectral quality in comparison to VDAC1 incorporated into linear nanodiscs of a similar size. This study provides evidence that circularized MSP nanodiscs are a promising tool to facilitate high-resolution NMR studies of larger and challenging membrane proteins in a native lipid environment.
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Pozza A, Giraud F, Cece Q, Casiraghi M, Point E, Damian M, Le Bon C, Moncoq K, Banères JL, Lescop E, Catoire LJ. Exploration of the dynamic interplay between lipids and membrane proteins by hydrostatic pressure. Nat Commun 2022; 13:1780. [PMID: 35365643 PMCID: PMC8975810 DOI: 10.1038/s41467-022-29410-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 03/14/2022] [Indexed: 02/06/2023] Open
Abstract
Cell membranes represent a complex and variable medium in time and space of lipids and proteins. Their physico-chemical properties are determined by lipid components which can in turn influence the biological function of membranes. Here, we used hydrostatic pressure to study the close dynamic relationships between lipids and membrane proteins. Experiments on the β–barrel OmpX and the α–helical BLT2 G Protein-Coupled Receptor in nanodiscs of different lipid compositions reveal conformational landscapes intimately linked to pressure and lipids. Pressure can modify the conformational landscape of the membrane protein per se, but also increases the gelation of lipids, both being monitored simultaneously at high atomic resolution by NMR. Our study also clearly shows that a membrane protein can modulate, at least locally, the fluidity of the bilayer. The strategy proposed herein opens new perspectives to scrutinize the dynamic interplay between membrane proteins and their surrounding lipids. Direct information on the dynamic interplay between membrane proteins and lipids is scarce. Here the authors report a detailed description of these close relationships by combining lipid nanodiscs and high-pressure NMR. They report the link between pressure and lipid compositions to the conformational landscape of the β-barrel OmpX and the α-helical BLT2 G Protein-Coupled Receptor in nanodiscs.
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Affiliation(s)
- Alexandre Pozza
- Laboratoire de Biologie Physico-Chimique des Protéines Membranaires, UMR 7099, CNRS/Université de Paris, Institut de Biologie Physico-Chimique (IBPC, FRC 550), 75005, Paris, France
| | - François Giraud
- Institut de Chimie des Substances Naturelles (ICSN), CNRS UPR 2301, Université Paris-Saclay, 91198, Gif-sur-Yvette, France
| | - Quentin Cece
- Laboratoire de Biologie Physico-Chimique des Protéines Membranaires, UMR 7099, CNRS/Université de Paris, Institut de Biologie Physico-Chimique (IBPC, FRC 550), 75005, Paris, France.,Laboratoire Cibles Thérapeutiques et Conception de Médicaments (CiTCoM), UMR 8038, CNRS/Université de Paris, Faculté de Pharmacie, 75270, Paris, Cedex 06, France
| | - Marina Casiraghi
- Laboratoire de Biologie Physico-Chimique des Protéines Membranaires, UMR 7099, CNRS/Université de Paris, Institut de Biologie Physico-Chimique (IBPC, FRC 550), 75005, Paris, France.,Department of Molecular and Cellular Physiology, Stanford University School of Medicine, 94305, Stanford, CA, USA
| | - Elodie Point
- Laboratoire de Biologie Physico-Chimique des Protéines Membranaires, UMR 7099, CNRS/Université de Paris, Institut de Biologie Physico-Chimique (IBPC, FRC 550), 75005, Paris, France
| | - Marjorie Damian
- Institut des Biomolécules Max Mousseron (IBMM), Université de Montpellier, CNRS, ENSCM, Pôle Chimie Balard Recherche, 34293, Montpellier, cedex 5, France
| | - Christel Le Bon
- Laboratoire de Biologie Physico-Chimique des Protéines Membranaires, UMR 7099, CNRS/Université de Paris, Institut de Biologie Physico-Chimique (IBPC, FRC 550), 75005, Paris, France
| | - Karine Moncoq
- Laboratoire de Biologie Physico-Chimique des Protéines Membranaires, UMR 7099, CNRS/Université de Paris, Institut de Biologie Physico-Chimique (IBPC, FRC 550), 75005, Paris, France
| | - Jean-Louis Banères
- Institut des Biomolécules Max Mousseron (IBMM), Université de Montpellier, CNRS, ENSCM, Pôle Chimie Balard Recherche, 34293, Montpellier, cedex 5, France
| | - Ewen Lescop
- Institut de Chimie des Substances Naturelles (ICSN), CNRS UPR 2301, Université Paris-Saclay, 91198, Gif-sur-Yvette, France.
| | - Laurent J Catoire
- Laboratoire de Biologie Physico-Chimique des Protéines Membranaires, UMR 7099, CNRS/Université de Paris, Institut de Biologie Physico-Chimique (IBPC, FRC 550), 75005, Paris, France.
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Mbikay M, Chrétien M. Isoquercetin as an Anti-Covid-19 Medication: A Potential to Realize. Front Pharmacol 2022; 13:830205. [PMID: 35308240 PMCID: PMC8924057 DOI: 10.3389/fphar.2022.830205] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Accepted: 01/26/2022] [Indexed: 12/30/2022] Open
Abstract
Isoquercetin and quercetin are secondary metabolites found in a variety of plants, including edible ones. Isoquercetin is a monoglycosylated derivative of quercetin. When ingested, isoquercetin accumulates more than quercetin in the intestinal mucosa where it is converted to quercetin; the latter is absorbed into enterocytes, transported to the liver, released in circulation, and distributed to tissues, mostly as metabolic conjugates. Physiologically, isoquercetin and quercetin exhibit antioxidant, anti-inflammatory, immuno-modulatory, and anticoagulant activities. Generally isoquercetin is less active than quercetin in vitro and ex vivo, whereas it is equally or more active in vivo, suggesting that it is primarily a more absorbable precursor to quercetin, providing more favorable pharmacokinetics to the latter. Isoquercetin, like quercetin, has shown broad-spectrum antiviral activities, significantly reducing cell infection by influenza, Zika, Ebola, dengue viruses among others. This ability, together with their other physiological properties and their safety profile, has led to the proposition that administration of these flavonols could prevent infection by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), or arrest the progression to severity and lethality of resulting coronavirus disease of 2019 (Covid-19). In silico screening of small molecules for binding affinity to proteins involved SARS-CoV-2 life cycle has repeatedly situated quercetin and isoquercetin near to top of the list of likely effectors. If experiments in cells and animals confirm these predictions, this will provide additional justifications for the conduct of clinical trials to evaluate the prophylactic and therapeutic efficacy of these flavonols in Covid-19.
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Affiliation(s)
- Majambu Mbikay
- Functional Endoproteolysis Laboratory, Montreal Clinical Research Institute, Montreal, QC, Canada
| | - Michel Chrétien
- Functional Endoproteolysis Laboratory, Montreal Clinical Research Institute, Montreal, QC, Canada
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Levitan I. Evaluating membrane structure by Laurdan imaging: Disruption of lipid packing by oxidized lipids. CURRENT TOPICS IN MEMBRANES 2021; 88:235-256. [PMID: 34862028 DOI: 10.1016/bs.ctm.2021.10.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Impact of different lipids on membrane structure/lipid order is critical for multiple biological processes. Laurdan microscopy provides a unique tool to assess this property in heterogeneous biological membranes. This review describes the general principles of the approach and its application in model membranes and cells. It also provides an in-depth discussion of the insights obtained using Laurdan microscopy to evaluate the differential effects of cholesterol, oxysterols and oxidized phospholipids on lipid packing of ordered and disordered domains in vascular endothelial cells.
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Affiliation(s)
- Irena Levitan
- Division of Pulmonary and Critical Care, Department of Medicine, University of Illinois at Chicago, Chicago, IL, United States.
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Self-Propelled Motion Sensitive to the Chemical Structure of Amphiphilic Molecular Layer on an Aqueous Phase. MEMBRANES 2021; 11:membranes11110885. [PMID: 34832114 PMCID: PMC8618350 DOI: 10.3390/membranes11110885] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/23/2021] [Revised: 11/12/2021] [Accepted: 11/14/2021] [Indexed: 11/17/2022]
Abstract
Two novel amphiphiles, N-(3-nitrophenyl)stearamide (MANA) and N,N′-(4-nitro-1,3-phenylene)distearamide (OPANA), were synthesized by reacting nitroanilines with one or two equivalents of stearic acid. We investigated how the molecular structures of these compounds influenced the characteristics of a self-propelled camphor disk placed on a monolayer of the synthesized amphiphiles. Three types of motion were observed at different surface pressures (Π): continuous motion (Π < 4 mN m−1), deceleration (4 mN ≤ Π ≤ 20 mN m−1), and no motion (Π > 20 mN m−1). The speed of the motion of the camphor disks was inversely related to Π for both MANA and OPANA at the temperatures tested, when Π increased in the respective molecular layers under compression. The spectroscopic evidence from UV-Vis, NMR, and ESI-TOF-MS revealed that the dependence of the speed of the motion on Π originates from the intermolecular interactions that are present in the monolayers. This study suggests that it is possible to control the self-propelled motion by manipulating contributing factors at the molecular level.
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10
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Xie CZ, Chang SM, Mamontov E, Stingaciu LR, Chen YF. Uncoupling between the lipid membrane dynamics of differing hierarchical levels. Phys Rev E 2020; 101:012416. [PMID: 32069643 DOI: 10.1103/physreve.101.012416] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2019] [Indexed: 11/07/2022]
Abstract
Diverse biological functions of biomembranes are made possible by their rich dynamic behaviors across multiple scales. While the potential coupling between the dynamics of differing scales may underlie the machineries regulating the biomembrane-involving processes, the mechanism and even the existence of this coupling remain an open question, despite the latter being taken for granted. Via inelastic neutron scattering, we examined dynamics across multiple scales for the lipid membranes whose dynamic behaviors were perturbed by configurational changes at two membrane regions. Surprisingly, the dynamic behavior of individual lipid molecules and their collective motions were not always coupled. This suggests that the expected causal relation between the dynamics of the differing hierarchical levels does not exist and that an apparent coupling can emerge by manipulating certain membrane configurations. The findings provide insight on biomembrane modeling and how cells might individually or concertedly control the multiscale membrane dynamics to regulate their functions.
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Affiliation(s)
- Cheng-Zhi Xie
- Department of Chemical and Materials Engineering, National Central University, Taoyuan 32001, Taiwan
| | - Shih-Min Chang
- Department of Chemical and Materials Engineering, National Central University, Taoyuan 32001, Taiwan
| | - Eugene Mamontov
- Neutron Scattering Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, USA
| | - Laura R Stingaciu
- Neutron Scattering Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, USA
| | - Yi-Fan Chen
- Department of Chemical and Materials Engineering, National Central University, Taoyuan 32001, Taiwan
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11
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Alterations to the contents of plasma membrane structural lipids are associated with structural changes and compartmentalization in platelets in hypertension. Exp Cell Res 2019; 385:111692. [PMID: 31689412 DOI: 10.1016/j.yexcr.2019.111692] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2019] [Revised: 10/24/2019] [Accepted: 10/28/2019] [Indexed: 01/14/2023]
Abstract
Arterial hypertension (HTN) can lead to serious organ damage. Several mechanisms have been implicated in the pathogenesis of HTN including constitutive activation of platelets, which increases the risk of aggregation and clot formation. We recently demonstrated the plasma membranes of platelets from patients with HTN exhibit modified structural and physicochemical properties; Raman and Fourier transform infrared by attenuated total reflectance (FTIR-ATR) spectroscopy also indicated lipid content and protein structure alterations. This study aimed to precisely quantify the constituents of the main structural phospholipids and cholesterol in the plasma membranes of platelets from patients with HTN and normotensive individuals. We also assessed the consequence of these alterations on platelet structure and function. Liquid chromatography coupled to triple quadrupole mass spectrometry revealed the plasma membranes of HTN platelets contained less cholesterol and phosphatidylcholine, more phosphatidylserine and phosphatidylethanolamine and had similar sphingosine contents. Atomic force microscopy revealed HTN platelets exhibited increased surface roughness and more pleats. Transmission electron microscopy revealed diminution of the internal membranous structures in HTN platelets. Our findings strongly suggest plasma membrane lipid content alterations-including cholesterol depletion-occur in HTN, and these alterations may induce morphological and physiological abnormalities that participate in the functional changes associated with hypertension.
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Interaction of Trastuzumab with biomembrane models at air-water interfaces mimicking cancer cell surfaces. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 2019; 1861:182992. [DOI: 10.1016/j.bbamem.2019.05.014] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Revised: 05/06/2019] [Accepted: 05/21/2019] [Indexed: 12/17/2022]
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Makino N, Ganguly P, Elimban V, Dhalla NS. Sarcolemmal Alterations in Unloaded Rat Heart after Heterotopic Transplantation. Int J Angiol 2018; 27:196-201. [PMID: 30410290 DOI: 10.1055/s-0038-1673646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022] Open
Abstract
Following heterotopic transplantation, the rat heart undergoes atrophy and exhibits delayed cardiac relaxation without any changes in contraction and systolic Ca 2+ transients. Furthermore, the sarcoplasmic reticular Ca 2+ uptake and release activities were reduced and Ca 2+ influx through L-type Ca 2+ channels was increased in the atrophied heart. Since Ca 2+ movements at sarcolemma are intimately involved in the regulation of intracellular Ca 2+ concentration, the present study was undertaken to test if sarcolemma plays any role to maintain cardiac function in the atrophied heart.The characteristics of sarcolemmal Ca 2+ pump and Na + -Ca 2+ exchange activities were examined in 8 weeks heterotopically isotransplanted rat hearts which did not support hemodynamic load and underwent atrophy. Sarcolemmal ATP (adenosine triphosphate)-dependent Ca 2+ uptake and Ca 2+ -stimulated ATPase (adenosine triphosphatase) activities were increased without any changes in Na + -K + ATPase activities in the transplanted hearts. Although no alterations in the Na + -dependent Ca 2+ uptake were evident, Na + -induced Ca 2+ release was increased in the transplanted heart sarcolemmal vesicles. The increase in Na + -induced Ca 2+ release was observed at different times of incubation as well as at 5, 20, and 40 mM Na + . The sarcolemma from transplanted hearts also showed higher contents of phosphatidic acid, sphingomyelin, and cholesterol.These results indicate that increases in the sarcolemmal, Ca 2+ transport activities in unloaded heart may provide an insight into adaptive mechanism to maintain normal contractile behavior of the atrophic heart.
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Affiliation(s)
- Naoki Makino
- Department of Molecular and Clinical Gerontology, Medical Institute of the Bioregulation, Kyushu University, Oita, Japan
| | - Paul Ganguly
- Department of Anatomy, College of Medicine, Alfaisal University, Riyadh, Kingdom of Saudi Arabia
| | - Vijayan Elimban
- Department of Physiology and Pathophysiology, Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, University of Manitoba, Winnipeg, Canada
| | - Naranjan S Dhalla
- Department of Physiology and Pathophysiology, Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, University of Manitoba, Winnipeg, Canada
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14
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Wang MC, Huang CE, Lin MH, Yang YH, Lu CH, Chen PT, Wu YY, Tsou HY, Hsu CC, Chen CC. Impacts of demographic and laboratory parameters on key hematological indices in an adult population of southern Taiwan: A cohort study. PLoS One 2018; 13:e0201708. [PMID: 30071080 PMCID: PMC6072090 DOI: 10.1371/journal.pone.0201708] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2017] [Accepted: 07/20/2018] [Indexed: 12/14/2022] Open
Abstract
Studies in Caucasians have shown that values of hematological indices could be affected by a wide variety of factors. However, parallel work in other ethnical populations, particularly from the Asia-Pacific region, is lacking. Therefore, we designed this study to explore the association between clinical/laboratory parameters and hemogram levels. Adult individuals who came to our hospital for health exams were screened. Information on demographics and laboratory profiles was obtained. We analyzed the impacts of these parameters on the variation of hemogram. Overall, 26,497 adults were included in the current analysis after excluding those with abnormal hemogram. Multivariate regression analysis showed increasing age and male gender negatively affected the number of platelets, whereas a higher serum apolipoprotein B level was associated with an elevated platelet count. Gender and serum albumin level were the major determinants of variation in hemoglobin level. A modestly increased white cell count was seen in men as well as individuals with elevated apolipoprotein B levels, but it was inversely correlated with changes in age and serum albumin levels. Conversely, some variables, although statistically significantly associated with the hematological indices, only provided a trivial explanation for the heterogeneity observed. We further established predictive models for the approximate estimation of hematological indices in healthy adults. Our data indicate that age, gender, and serum levels of apolipoprotein B and albumin affect hematological indices in various ways. We also demonstrate that variation in hemogram could be successfully predicted by a number of clinical and laboratory parameters.
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Affiliation(s)
- Ming-Chung Wang
- Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Cih-En Huang
- Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Meng-Hung Lin
- Center of Excellence for Chang Gung Research Datalink, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Yao-Hsu Yang
- Center of Excellence for Chang Gung Research Datalink, Chang Gung Memorial Hospital, Chiayi, Taiwan
- Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, Taipei, Taiwan
- School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Chang-Hsien Lu
- Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Ping-Tsung Chen
- Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Yu-Ying Wu
- Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Hsing-Yi Tsou
- Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Chia-Chen Hsu
- Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Chih-Cheng Chen
- Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan
- School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- * E-mail:
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15
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Mathew B, Srinivasan K, Pradeep J, Thomas T, Mandal AK. Suicidal behaviour is associated with decreased esterified cholesterol in plasma and membrane fluidity of platelets. Asian J Psychiatr 2018; 32:105-109. [PMID: 29222984 DOI: 10.1016/j.ajp.2017.11.023] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2017] [Revised: 10/26/2017] [Accepted: 11/27/2017] [Indexed: 10/18/2022]
Abstract
BACKGROUND Altered cholesterol levels in body fluids and brain tissues have been shown to be associated with suicidal behaviour, violence and aggression. But the biological underpinnings of this association in the pathophysiology of suicide are not clear. Cholesterol plays a crucial role in maintaining the cellular membrane fluidity and alterations in cellular membrane fluidity may impair serotonergic neurotransmission in the central nervous system. METHODS We measured plasma esterified cholesterol and platelet membrane fluidity using fluorescence anisotropy and estimated flow activation energy which is a measure of order of membrane lipid bilayer in patients with recent suicidal attempt and compared with age and gender matched controls. RESULTS The plasma esterified cholesterol, platelet membrane fluidity and flow activation energy was found to be significantly lower in patients with recent suicidal attempts compared to controls. CONCLUSION Altered levels of plasma esterified cholesterol which is in equilibrium with membrane cholesterol might have resulted in decreased membrane fluidity and an increase in the order of membrane lipid bilayer. This might impair the serotonergic neurotransmission, which has been implicated in the pathophysiology of suicide.
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Affiliation(s)
- Boby Mathew
- Clinical Proteomics Unit, Division of Molecular Medicine, St. John's Research Institute, St. John's National Academy of Health Sciences, Bangalore, India
| | - Krishnamachari Srinivasan
- Department of Psychiatry, St. John's Medical College and Hospital, St. John's National Academy of Health Sciences, Bangalore, India
| | - Johnson Pradeep
- Department of Psychiatry, St. John's Medical College and Hospital, St. John's National Academy of Health Sciences, Bangalore, India
| | - Tinku Thomas
- Division of Epidemiology and Biostatistics, St. John's Research Institute, St. John's National Academy of Health Sciences, Bangalore, India
| | - Amit Kumar Mandal
- Clinical Proteomics Unit, Division of Molecular Medicine, St. John's Research Institute, St. John's National Academy of Health Sciences, Bangalore, India.
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16
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Li Q, Yang LZ. HEMOGLOBIN A1c LEVEL HIGHER THAN 9.05% CAUSES A SIGNIFICANT IMPAIRMENT OF ERYTHROCYTE DEFORMABILITY IN DIABETES MELLITUS. ACTA ENDOCRINOLOGICA-BUCHAREST 2018; 14:66-75. [PMID: 31149238 DOI: 10.4183/aeb.2018.66] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Context Clinical studies demonstrated erythrocyte deformability (ED) is impaired in diabetic patients and described the correlations between HbA1c and ED. Few studies further investigated what an exact elevated HbA1c level linked to the impairment of ED in diabetes. Objective This study was to determine a cut-off point of HbA1c level leading to the impairment of ED in patients with diabetes. Design This was a retrospective observational study. ROC curve analysis was used to determine an optimal cut-off value of HbA1c for the increasing HSRV. Subjects and Methods In this study, 300 type 2 diabetic patients were enrolled. The whole blood viscosity was measured. High shear reductive viscosity (HSRV) was used to indirectly estimate ED. Based on the obtained cut-off value and glycemic control criteria for HbA1c, we divided all the cases into different groups to further confirm the accuracy of the cut-off value. Results In 300 patients, ROC curve illustrated that 9.05% was the optimal cut-off value as a predictor of the increasing HSRV. And higher odds ratio (OR) for significant decrease in ED was seen in the patients with HbA1c >9.05% compared to those with HbA1c≤9.05% (OR: 3.78, 95% CI: 2.08-6.87). HSRV increased significantly in patients with HbA1c level >9.05% in comparison to patients with HbA1c levels <6.5% between 6.5 and 8.0% and between 8.0 and 9.05%. Conclusion ED decreased significantly in diabetic patients as soon as HbA1c level was higher than 9.05%.
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Affiliation(s)
- Q Li
- Shanghai Ninth People's Hospital affiliated Shanghai Jiaotong University School of Medicine, Division of Endocrinology and Metabolism, Shanghai, China
| | - L Z Yang
- Shanghai Ninth People's Hospital affiliated Shanghai Jiaotong University School of Medicine, Division of Endocrinology and Metabolism, Shanghai, China
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17
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Notarnicola M, Caruso MG, Tutino V, Bonfiglio C, Cozzolongo R, Giannuzzi V, De Nunzio V, De Leonardis G, Abbrescia DI, Franco I, Intini V, Mirizzi A, Osella AR. Significant decrease of saturation index in erythrocytes membrane from subjects with non-alcoholic fatty liver disease (NAFLD). Lipids Health Dis 2017; 16:160. [PMID: 28830448 PMCID: PMC5568099 DOI: 10.1186/s12944-017-0552-0] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2017] [Accepted: 08/15/2017] [Indexed: 12/03/2022] Open
Abstract
Background The lipidomic profiling of erythrocyte membranes is expected to provide a peculiar scenario at molecular level of metabolic and nutritional pathways which may influence the lipid balance and the adaptation and homeostasis of the organism. Considering that lipid accumulation in the cell is important in promoting tissue inflammation, the purpose of this study is to analyze the fatty acid profile in red blood cell membranes of patients with Non-Alcoholic Fatty Liver Disease (NAFLD), in order to identify and validate membrane profiles possibly associated with the degree of hepatic damage. Methods This work presents data obtained at baseline from 101 subjects that participated to a nutritional trial (registration number: NCT02347696) enrolling consecutive subjects with NAFLD. Diagnosis of liver steatosis was performed by using vibration-controlled elastography implemented on FibroScan. Fatty acids, extracted from phospholipids of erythrocyte membranes, were quantified by gas chromatography method. Results The subjects with severe NAFLD showed a significant decrease of the ratio of stearic acid to oleic acid (saturation index, SI) compared to controls, 1.281 ± 0.31 vs 1.5 ± 0.29, respectively. Low levels of SI in red blood cell membranes, inversely associated with degree of liver damage, suggest that an impairment of circulating cell membrane structure can reflect modifications that take place in the liver. Subjects with severe NAFLDalso showed higher levels of elongase 5 enzymatic activity, evaluated as vaccenic acid to palmitoleic acid ratio. Conclusions Starting from these evidences, our findings show the importance of lipidomic approach in the diagnosis and the staging of NAFLD.
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Affiliation(s)
- Maria Notarnicola
- National Institute of Gastroenterology "S. de Bellis" Research Hospital, 70013 Castellana Grotte, Bari, Italy. .,Laboratory of Nutritional Biochemistry, National Institute of Gastroenterology "S. de Bellis", Research Hospital, Castellana Grotte, Bari, Italy.
| | - Maria Gabriella Caruso
- National Institute of Gastroenterology "S. de Bellis" Research Hospital, 70013 Castellana Grotte, Bari, Italy
| | - Valeria Tutino
- National Institute of Gastroenterology "S. de Bellis" Research Hospital, 70013 Castellana Grotte, Bari, Italy
| | - Caterina Bonfiglio
- National Institute of Gastroenterology "S. de Bellis" Research Hospital, 70013 Castellana Grotte, Bari, Italy
| | - Raffaele Cozzolongo
- National Institute of Gastroenterology "S. de Bellis" Research Hospital, 70013 Castellana Grotte, Bari, Italy
| | - Vito Giannuzzi
- National Institute of Gastroenterology "S. de Bellis" Research Hospital, 70013 Castellana Grotte, Bari, Italy
| | - Valentina De Nunzio
- National Institute of Gastroenterology "S. de Bellis" Research Hospital, 70013 Castellana Grotte, Bari, Italy
| | - Giampiero De Leonardis
- National Institute of Gastroenterology "S. de Bellis" Research Hospital, 70013 Castellana Grotte, Bari, Italy
| | - Daniela I Abbrescia
- National Institute of Gastroenterology "S. de Bellis" Research Hospital, 70013 Castellana Grotte, Bari, Italy
| | - Isabella Franco
- National Institute of Gastroenterology "S. de Bellis" Research Hospital, 70013 Castellana Grotte, Bari, Italy
| | - Vincenza Intini
- National Institute of Gastroenterology "S. de Bellis" Research Hospital, 70013 Castellana Grotte, Bari, Italy
| | - Antonella Mirizzi
- National Institute of Gastroenterology "S. de Bellis" Research Hospital, 70013 Castellana Grotte, Bari, Italy
| | - Alberto R Osella
- National Institute of Gastroenterology "S. de Bellis" Research Hospital, 70013 Castellana Grotte, Bari, Italy
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18
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Liu Q, Lichtenstein AH, Matthan NR, Howe CJ, Allison MA, Howard BV, Martin LW, Valdiviezo C, Manson JE, Liu S, Eaton CB. Higher Lipophilic Index Indicates Higher Risk of Coronary Heart Disease in Postmenopausal Women. Lipids 2017; 52:687-702. [PMID: 28689316 PMCID: PMC6903800 DOI: 10.1007/s11745-017-4276-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2017] [Accepted: 06/19/2017] [Indexed: 11/29/2022]
Abstract
Fatty acids (FAs) are essential components of cell membranes and play an integral role in membrane fluidity. The lipophilic index [LI, defined as the sum of the products between FA levels and melting points (°C), divided by the total amount of FA: [Formula: see text]] is thought to reflect membrane and lipoprotein fluidity and may be associated with the risk of coronary heart disease (CHD). Therefore, we examined the associations of dietary and plasma phospholipid (PL) LI with CHD risk among postmenopausal women. We determined dietary LI for the cohort with completed baseline food frequency questionnaires and free of prevalent cardiovascular diseases in the Women's Health Initiative (WHI) observational study (N = 85,563). We additionally determined plasma PL LI in a matched case-control study (N = 2428) nested within the WHI observational cohort study. Cox proportional hazard regression and multivariable conditional logistic regression were used to calculate HRs/ORs for CHD risk between quartiles of LI after adjusting for potential sources of confounding and selection bias. Higher dietary LI in the cohort study and plasma PL LI in the case-control study were significantly associated with increased risk of CHD: HR = 1.18 (95% CI 1.07-1.31, P for trend <0.01) and OR = 1.76 (95% CI 1.33-2.33, P for trend <0.01) comparing extreme quartiles and adjusting for potential confounders. These associations still persisted after adjusting for the polyunsaturated to saturated fat ratio. Our study indicated that higher LI based on either dietary or plasma measurements, representing higher FA lipophilicity, was associated with elevated risk of CHD among postmenopausal women.
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Affiliation(s)
- Qing Liu
- Department of Epidemiology, School of Public Health, Brown University, Providence, RI, USA
| | - Alice H Lichtenstein
- Jean Mayer USDA Human Nutrition Research Center ON Aging, Tufts University, Boston, MA, USA
| | - Nirupa R Matthan
- Jean Mayer USDA Human Nutrition Research Center ON Aging, Tufts University, Boston, MA, USA
| | - Chanelle J Howe
- Department of Epidemiology, School of Public Health, Brown University, Providence, RI, USA
| | - Matthew A Allison
- University of California, San Diego, La Jolla, CA, USA
- VA San Diego Healthcare System, San Diego, CA, USA
| | - Barbara V Howard
- MedStar Health Research Institute, Hyattsville, MD, USA
- Georgetown-Howard Universities Center for Clinical and Translational Science, Washington, DC, USA
| | - Lisa W Martin
- Division of Cardiology, George Washington University School of Medicine and Health Sciences, Washington, DC, USA
| | - Carolina Valdiviezo
- Medstar Washington Hospital Center and Georgetown University School of Medicine, Washington, DC, USA
| | - JoAnn E Manson
- Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Simin Liu
- Department of Epidemiology, School of Public Health, Brown University, Providence, RI, USA
| | - Charles B Eaton
- Department of Epidemiology, School of Public Health, Brown University, Providence, RI, USA.
- Center for Primary Care and Prevention, Memorial Hospital of Rhode Island, 111 Brewster Street, Pawtucket, RI, 02680, USA.
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19
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Tsang KY, Lai YC, Chiang YW, Chen YF. Coupling of lipid membrane elasticity and in-plane dynamics. Phys Rev E 2017; 96:012410. [PMID: 29347274 DOI: 10.1103/physreve.96.012410] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2017] [Indexed: 11/07/2022]
Abstract
Biomembranes exhibit liquid and solid features concomitantly with their in-plane fluidity and elasticity tightly regulated by cells. Here, we present experimental evidence supporting the existence of the dynamics-elasticity correlations for lipid membranes and propose a mechanism involving molecular packing densities to explain them. This paper thereby unifies, at the molecular level, the aspects of the continuum mechanics long used to model the two membrane features. This ultimately may elucidate the universal physical principles governing the cellular phenomena involving biomembranes.
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Affiliation(s)
- Kuan-Yu Tsang
- Department of Chemical and Materials Engineering, National Central University, Taoyuan 32001, Taiwan
| | - Yei-Chen Lai
- Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan
| | - Yun-Wei Chiang
- Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan
| | - Yi-Fan Chen
- Department of Chemical and Materials Engineering, National Central University, Taoyuan 32001, Taiwan
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20
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D’Auria L, Reiter C, Ward E, Moyano AL, Marshall MS, Nguyen D, Scesa G, Hauck Z, van Breemen R, Givogri MI, Bongarzone ER. Psychosine enhances the shedding of membrane microvesicles: Implications in demyelination in Krabbe's disease. PLoS One 2017; 12:e0178103. [PMID: 28531236 PMCID: PMC5439731 DOI: 10.1371/journal.pone.0178103] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2017] [Accepted: 05/06/2017] [Indexed: 12/22/2022] Open
Abstract
In prior studies, our laboratory showed that psychosine accumulates and disrupts lipid rafts in brain membranes of Krabbe’s disease. A model of lipid raft disruption helped explaining psychosine’s effects on several signaling pathways important for oligodendrocyte survival and differentiation but provided more limited insight in how this sphingolipid caused demyelination. Here, we have studied how this cationic inverted coned lipid affects the fluidity, stability and structure of myelin and plasma membranes. Using a combination of cutting-edge imaging techniques in non-myelinating (red blood cell), and myelinating (oligodendrocyte) cell models, we show that psychosine is sufficient to disrupt sphingomyelin-enriched domains, increases the rigidity of localized areas in the plasma membrane, and promotes the shedding of membranous microvesicles. The same physicochemical and structural changes were measured in myelin membranes purified from the mutant mouse Twitcher, a model for Krabbe’s disease. Areas of higher rigidity were measured in Twitcher myelin and correlated with higher levels of psychosine and of myelin microvesiculation. These results expand our previous analyses and support, for the first time a pathogenic mechanism where psychosine’s toxicity in Krabbe disease involves deregulation of cell signaling not only by disruption of membrane rafts, but also by direct local destabilization and fragmentation of the membrane through microvesiculation. This model of membrane disruption may be fundamental to introduce focal weak points in the myelin sheath, and consequent diffuse demyelination in this leukodystrophy, with possible commonality to other demyelinating disorders.
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Affiliation(s)
- Ludovic D’Auria
- Department of Anatomy and Cell Biology, College of Medicine, University of Illinois, Chicago, Illinois, United States of America
| | - Cory Reiter
- Department of Anatomy and Cell Biology, College of Medicine, University of Illinois, Chicago, Illinois, United States of America
| | - Emma Ward
- Department of Anatomy and Cell Biology, College of Medicine, University of Illinois, Chicago, Illinois, United States of America
| | - Ana Lis Moyano
- Department of Anatomy and Cell Biology, College of Medicine, University of Illinois, Chicago, Illinois, United States of America
| | - Michael S. Marshall
- Department of Anatomy and Cell Biology, College of Medicine, University of Illinois, Chicago, Illinois, United States of America
| | - Duc Nguyen
- Department of Anatomy and Cell Biology, College of Medicine, University of Illinois, Chicago, Illinois, United States of America
| | - Giuseppe Scesa
- Department of Anatomy and Cell Biology, College of Medicine, University of Illinois, Chicago, Illinois, United States of America
| | - Zane Hauck
- Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois, Chicago, Illinois, United States of America
| | - Richard van Breemen
- Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois, Chicago, Illinois, United States of America
| | - Maria I. Givogri
- Department of Anatomy and Cell Biology, College of Medicine, University of Illinois, Chicago, Illinois, United States of America
| | - Ernesto R. Bongarzone
- Department of Anatomy and Cell Biology, College of Medicine, University of Illinois, Chicago, Illinois, United States of America
- Departamento de Química Biologica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina
- * E-mail:
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21
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Xu H, Ärnlöv J, Sandhagen B, Risérus U, Lindholm B, Lind L, Carrero JJ. Lipophilic index, kidney function, and kidney function decline. Nutr Metab Cardiovasc Dis 2016; 26:1096-1103. [PMID: 27773469 DOI: 10.1016/j.numecd.2016.09.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2016] [Revised: 08/17/2016] [Accepted: 09/04/2016] [Indexed: 10/21/2022]
Abstract
BACKGROUND AND AIMS Unhealthy dietary fats are associated with faster kidney function decline. The cell membrane composition of phospholipid fatty acids (FAs) is a determinant of membrane fluidity and rheological properties. These properties, which have been linked to kidney damage, are thought to be reflected by the lipophilic index (LI). We prospectively investigated the associations of LI with kidney function and its decline. METHODS AND RESULTS Observational study from the Prospective Investigation of Vasculature in Uppsala Seniors including 975 men and women with plasma phospholipid FAs composition and cystatin-C estimate glomerular filtration rate (eGFR). Of these, 780 attended re-examination after 5 years, and eGFR changes were assessed. Participants with a 5-year eGFR reduction ≥30% were considered chronic kidney disease (CKD) progressors (n = 198). LI was calculated as the sum of the products of the FA proportions with the respective FAs melting points. Blood rheology/viscosity measurements were performed in a random subsample of 559 subjects at baseline. Increased LI showed a statistically significant but overall weak association with blood, plasma viscosity (both Spearman rho = 0.16, p < 0.01), and erythrocyte deformability (rho = -0.09, p < 0.05). In cross-sectional analyses, LI associated with lower eGFR (regression coefficient 3.00 ml/min/1.73 m2 1-standard deviation (SD) increment in LI, 95% CI: -4.31, -1.69, p < 0.001). In longitudinal analyses, LI associated with a faster eGFR decline (-2.13 [95% CI -3.58, -0.69] ml/min/1.73 m2, p < 0.01) and with 32% increased odds of CKD progression (adjusted OR 1.32 [95%, CI 1.05-1.65]). CONCLUSIONS A high LI was associated with lower kidney function, kidney function decline, and CKD progression.
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Affiliation(s)
- H Xu
- Divisions of Renal Medicine and Baxter Novum, Karolinska Institutet, Stockholm, Sweden
| | - J Ärnlöv
- Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden; School of Health and Social Studies, Dalarna University, Falun, Sweden
| | - B Sandhagen
- Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden
| | - U Risérus
- Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden
| | - B Lindholm
- Divisions of Renal Medicine and Baxter Novum, Karolinska Institutet, Stockholm, Sweden
| | - L Lind
- Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden
| | - J J Carrero
- Divisions of Renal Medicine and Baxter Novum, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
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22
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Thacker SG, Zarzour A, Chen Y, Alcicek MS, Freeman LA, Sviridov DO, Demosky SJ, Remaley AT. High-density lipoprotein reduces inflammation from cholesterol crystals by inhibiting inflammasome activation. Immunology 2016; 149:306-319. [PMID: 27329564 PMCID: PMC5046053 DOI: 10.1111/imm.12638] [Citation(s) in RCA: 79] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2016] [Revised: 05/17/2016] [Accepted: 06/07/2016] [Indexed: 12/26/2022] Open
Abstract
Interleukin-1β (IL-1β), a potent pro-inflammatory cytokine, has been implicated in many diseases, including atherosclerosis. Activation of IL-1β is controlled by a multi-protein complex, the inflammasome. The exact initiating event in atherosclerosis is unknown, but recent work has demonstrated that cholesterol crystals (CC) may promote atherosclerosis development by activation of the inflammasome. High-density lipoprotein (HDL) has consistently been shown to be anti-atherogenic and to have anti-inflammatory effects, but its mechanism of action is unclear. We demonstrate here that HDL is able to suppress IL-1β secretion in response to cholesterol crystals in THP-1 cells and in human-monocyte-derived macrophages. HDL is able to blunt inflammatory monocyte cell recruitment in vivo following intraperitoneal CC injection in mice. HDL appears to modulate inflammasome activation in several ways. It reduces the loss of lysosomal membrane integrity following the phagocytosis of CC, but the major mechanism for the suppression of inflammasome activation by HDL is decreased expression of pro-IL-1β and NLRP3, and reducing caspase-1 activation. In summary, we have described a novel anti-inflammatory effect of HDL, namely its ability to suppress inflammasome activation by CC by modulating the expression of several key components of the inflammasome.
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Affiliation(s)
- Seth G Thacker
- Lipoprotein Metabolism Section, Cardiovascular-Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Abdalrahman Zarzour
- Lipoprotein Metabolism Section, Cardiovascular-Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Ye Chen
- Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Mustafa S Alcicek
- Lipoprotein Metabolism Section, Cardiovascular-Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Lita A Freeman
- Lipoprotein Metabolism Section, Cardiovascular-Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Dennis O Sviridov
- Lipoprotein Metabolism Section, Cardiovascular-Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Stephen J Demosky
- Lipoprotein Metabolism Section, Cardiovascular-Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Alan T Remaley
- Lipoprotein Metabolism Section, Cardiovascular-Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
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23
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Hong JY, Yang GE, Ko Y, Park YB, Sim YS, Park SH, Lee CY, Jung KS, Lee MG. Changes in cholesterol level correlate with the course of pulmonary nontuberculous mycobacterial disease. J Thorac Dis 2016; 8:2885-2894. [PMID: 27867565 DOI: 10.21037/jtd.2016.10.75] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
BACKGROUND Nutritional assessment is important in patients with pulmonary nontuberculous mycobacterial (PNTM) disease. The therapeutic effect of a cholesterol-rich diet in tuberculosis (TB) patients has been demonstrated, but the role of cholesterol in PNTM disease is unclear. This study evaluated the sequential changes in nutritional markers, including cholesterol, total lymphocyte count and visceral fat volume, according to the PNTM disease course. METHODS This was an age-, sex- and number of comorbid diseases-matched case-control analysis of 89 patients with PNTM disease and 356 controls, who were participants in a Korean national survey. RESULTS The median body mass index (BMI) and cholesterol level in the PNTM group [BMI =19.7 kg/m2; interquartile range (IQR): 17.8-21.6; cholesterol: 159 mg/dL; IQR, 135-185] were lower than those in controls (BMI: 23.1 kg/m2; IQR, 21.3-25.3; cholesterol: 188 mg/dL; IQR, 164-217; both P<0.001). In a multivariate analysis, Age more than 70 years (OR =3.38; 95% CI: 1.13-10.15, P=0.029), BMI <19.5 kg/m2 (OR =5.09; 95% CI: 1.67-15.48; P=0.004) and cavitary lesions (OR: 3.86; 95% CI: 1.30-11.47; P=0.015) were independently associated with extensive pulmonary lesions involving more than four lobes. The total cholesterol level, total lymphocyte count showed a tendency to decrease in PNTM patients with disease progression (both, P value <0.05), but not in those with a stable disease course. A decrease in cholesterol concentration of >20 mg/dL and a decrease in lymphocyte count more than 200/µL were predictive factors for disease progression (cholesterol: OR =10.50, 95% CI: 2.51-43.98, P=0.001; lymphocyte count: OR =5.32, 95% CI: 1.46-19.35, P=0.011). CONCLUSIONS These findings suggest that the change in cholesterol level may be a marker of disease progression in patients with PNTM disease.
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Affiliation(s)
- Ji Young Hong
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Chuncheon Sacred Heart Hospital, Hallym University Medical Center, Chuncheon, Gangwon-do, Republic of Korea;; Lung Research Institute of Hallym University College of Medicine, Seoul, Republic of Korea
| | - Go Eun Yang
- Department of Radiology, Chuncheon Sacred Heart Hospital, Hallym University Medical Center, Chuncheon, Gangwon-do, Republic of Korea
| | - Yousang Ko
- Lung Research Institute of Hallym University College of Medicine, Seoul, Republic of Korea;; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, Republic of Korea
| | - Yong Bum Park
- Lung Research Institute of Hallym University College of Medicine, Seoul, Republic of Korea;; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, Republic of Korea
| | - Yun Su Sim
- Lung Research Institute of Hallym University College of Medicine, Seoul, Republic of Korea;; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Hallym University Kangnam Sacred Heart Hospital, Seoul, Korea
| | - Sung Hoon Park
- Lung Research Institute of Hallym University College of Medicine, Seoul, Republic of Korea;; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea
| | - Chang Youl Lee
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Chuncheon Sacred Heart Hospital, Hallym University Medical Center, Chuncheon, Gangwon-do, Republic of Korea;; Lung Research Institute of Hallym University College of Medicine, Seoul, Republic of Korea
| | - Ki-Suck Jung
- Lung Research Institute of Hallym University College of Medicine, Seoul, Republic of Korea;; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea
| | - Myung Goo Lee
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Chuncheon Sacred Heart Hospital, Hallym University Medical Center, Chuncheon, Gangwon-do, Republic of Korea;; Lung Research Institute of Hallym University College of Medicine, Seoul, Republic of Korea
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24
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Effects of Mesalazine on Morphological and Functional Changes in the Indomethacin-Induced Inflammatory Bowel Disease (Rat Model of Crohn's Disease). Pathol Oncol Res 2016; 23:41-46. [PMID: 27294352 DOI: 10.1007/s12253-016-0069-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2015] [Accepted: 04/27/2016] [Indexed: 10/21/2022]
Abstract
Morphological and functional changes have been investigated in the rat model of Crohn's disease. The inflammatory bowel disease was induced by indomethacin (1 × 10 mg/kg s.c. for 3 days). Morphological alterations were evaluated by macroscopic scoring system and on the base of histological changes in the small intestine. Functional activities were studied by determination of the intestinal and hepatic elimination of p-Nitrophenol (PNP) and its metabolites (PNP-glucuronide: PNP-G and PNP-sulfate: PNP-S) during the luminal perfusion of PNP. It was found that the indomethacin induced severe macroscopic changes (hyperaemia, petechia, bleeding, erosions, ulcerations) and significant histological alterations in the small intestine of rats which were definitely inhibited by mesalazine (1000 mg/kg by gastric tube for 3 days). Disappearance of PNP from the luminal perfusion solution was diminished by indomethacin which was corrected by administration of mesalazine. Significant depression was found in the luminal appearance of PNP metabolites by giving of indomethacin and these alterations could not be compensated by mesalazine.Hepatic elimination of PNP (biliary excretion of PNP and its metabolites) was decreased definitely by indomethacin which was - at least partly - compensated by mesalazine.The findings of the present study suggest that the indomethacin-induced inflammation in the small intestine represents a useful rat model of Crohn's disease. Morphological and functional alterations caused by indomethacin can be compensated by mesalazine.
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25
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Unruh D, Srinivasan R, Benson T, Haigh S, Coyle D, Batra N, Keil R, Sturm R, Blanco V, Palascak M, Franco RS, Tong W, Chatterjee T, Hui DY, Davidson WS, Aronow BJ, Kalfa T, Manka D, Peairs A, Blomkalns A, Fulton DJ, Brittain JE, Weintraub NL, Bogdanov VY. Red Blood Cell Dysfunction Induced by High-Fat Diet: Potential Implications for Obesity-Related Atherosclerosis. Circulation 2015; 132:1898-908. [PMID: 26467254 PMCID: PMC4772773 DOI: 10.1161/circulationaha.115.017313] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2015] [Accepted: 08/28/2015] [Indexed: 12/31/2022]
Abstract
BACKGROUND High-fat diet (HFD) promotes endothelial dysfunction and proinflammatory monocyte activation, which contribute to atherosclerosis in obesity. We investigated whether HFD also induces the dysfunction of red blood cells (RBCs), which serve as a reservoir for chemokines via binding to Duffy antigen receptor for chemokines (DARC). METHODS AND RESULTS A 60% HFD for 12 weeks, which produced only minor changes in lipid profile in C57/BL6 mice, markedly augmented the levels of monocyte chemoattractant protein-1 bound to RBCs, which in turn stimulated macrophage migration through an endothelial monolayer. Levels of RBC-bound KC were also increased by HFD. These effects of HFD were abolished in DARC(-/-) mice. In RBCs from HFD-fed wild-type and DARC(-/-) mice, levels of membrane cholesterol and phosphatidylserine externalization were increased, fostering RBC-macrophage inflammatory interactions and promoting macrophage phagocytosis in vitro. When labeled ex vivo and injected into wild-type mice, RBCs from HFD-fed mice exhibited ≈3-fold increase in splenic uptake. Finally, RBCs from HFD-fed mice induced increased macrophage adhesion to the endothelium when they were incubated with isolated aortic segments, indicating endothelial activation. CONCLUSIONS RBC dysfunction, analogous to endothelial dysfunction, occurs early during diet-induced obesity and may serve as a mediator of atherosclerosis. These findings may have implications for the pathogenesis of atherosclerosis in obesity, a worldwide epidemic.
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Affiliation(s)
- Dusten Unruh
- From Hematology/Oncology, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.U., R.S., R.K., R.S., V.B., M.P., R.S.F., V.Y.B.); Vascular Biology Center, Georgia Regents University, Augusta, GA (T.B., S.H., T.C., D.J.F., N.L.W.); Cardiovascular Diseases, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.C., N.B., W.T., D.M.); Department of Nutritional Sciences, College of Allied Health Sciences, University of Cincinnati, OH (D.C., A.P.); Department of Pathology, College of Medicine, University of Cincinnati, OH (D.Y.H., W.S.D.); Biomedical Informatics and Developmental Biology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (B.J.A.); Experimental Hematology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (T.K.); Hemoshear LLC, Charlottesville, VA (D.M.); and Department of Emergency Medicine, University of Texas Southwestern Medical Center, Dallas (A.B.)
| | - Ramprasad Srinivasan
- From Hematology/Oncology, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.U., R.S., R.K., R.S., V.B., M.P., R.S.F., V.Y.B.); Vascular Biology Center, Georgia Regents University, Augusta, GA (T.B., S.H., T.C., D.J.F., N.L.W.); Cardiovascular Diseases, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.C., N.B., W.T., D.M.); Department of Nutritional Sciences, College of Allied Health Sciences, University of Cincinnati, OH (D.C., A.P.); Department of Pathology, College of Medicine, University of Cincinnati, OH (D.Y.H., W.S.D.); Biomedical Informatics and Developmental Biology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (B.J.A.); Experimental Hematology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (T.K.); Hemoshear LLC, Charlottesville, VA (D.M.); and Department of Emergency Medicine, University of Texas Southwestern Medical Center, Dallas (A.B.)
| | - Tyler Benson
- From Hematology/Oncology, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.U., R.S., R.K., R.S., V.B., M.P., R.S.F., V.Y.B.); Vascular Biology Center, Georgia Regents University, Augusta, GA (T.B., S.H., T.C., D.J.F., N.L.W.); Cardiovascular Diseases, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.C., N.B., W.T., D.M.); Department of Nutritional Sciences, College of Allied Health Sciences, University of Cincinnati, OH (D.C., A.P.); Department of Pathology, College of Medicine, University of Cincinnati, OH (D.Y.H., W.S.D.); Biomedical Informatics and Developmental Biology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (B.J.A.); Experimental Hematology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (T.K.); Hemoshear LLC, Charlottesville, VA (D.M.); and Department of Emergency Medicine, University of Texas Southwestern Medical Center, Dallas (A.B.)
| | - Stephen Haigh
- From Hematology/Oncology, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.U., R.S., R.K., R.S., V.B., M.P., R.S.F., V.Y.B.); Vascular Biology Center, Georgia Regents University, Augusta, GA (T.B., S.H., T.C., D.J.F., N.L.W.); Cardiovascular Diseases, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.C., N.B., W.T., D.M.); Department of Nutritional Sciences, College of Allied Health Sciences, University of Cincinnati, OH (D.C., A.P.); Department of Pathology, College of Medicine, University of Cincinnati, OH (D.Y.H., W.S.D.); Biomedical Informatics and Developmental Biology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (B.J.A.); Experimental Hematology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (T.K.); Hemoshear LLC, Charlottesville, VA (D.M.); and Department of Emergency Medicine, University of Texas Southwestern Medical Center, Dallas (A.B.)
| | - Danielle Coyle
- From Hematology/Oncology, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.U., R.S., R.K., R.S., V.B., M.P., R.S.F., V.Y.B.); Vascular Biology Center, Georgia Regents University, Augusta, GA (T.B., S.H., T.C., D.J.F., N.L.W.); Cardiovascular Diseases, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.C., N.B., W.T., D.M.); Department of Nutritional Sciences, College of Allied Health Sciences, University of Cincinnati, OH (D.C., A.P.); Department of Pathology, College of Medicine, University of Cincinnati, OH (D.Y.H., W.S.D.); Biomedical Informatics and Developmental Biology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (B.J.A.); Experimental Hematology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (T.K.); Hemoshear LLC, Charlottesville, VA (D.M.); and Department of Emergency Medicine, University of Texas Southwestern Medical Center, Dallas (A.B.)
| | - Neil Batra
- From Hematology/Oncology, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.U., R.S., R.K., R.S., V.B., M.P., R.S.F., V.Y.B.); Vascular Biology Center, Georgia Regents University, Augusta, GA (T.B., S.H., T.C., D.J.F., N.L.W.); Cardiovascular Diseases, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.C., N.B., W.T., D.M.); Department of Nutritional Sciences, College of Allied Health Sciences, University of Cincinnati, OH (D.C., A.P.); Department of Pathology, College of Medicine, University of Cincinnati, OH (D.Y.H., W.S.D.); Biomedical Informatics and Developmental Biology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (B.J.A.); Experimental Hematology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (T.K.); Hemoshear LLC, Charlottesville, VA (D.M.); and Department of Emergency Medicine, University of Texas Southwestern Medical Center, Dallas (A.B.)
| | - Ryan Keil
- From Hematology/Oncology, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.U., R.S., R.K., R.S., V.B., M.P., R.S.F., V.Y.B.); Vascular Biology Center, Georgia Regents University, Augusta, GA (T.B., S.H., T.C., D.J.F., N.L.W.); Cardiovascular Diseases, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.C., N.B., W.T., D.M.); Department of Nutritional Sciences, College of Allied Health Sciences, University of Cincinnati, OH (D.C., A.P.); Department of Pathology, College of Medicine, University of Cincinnati, OH (D.Y.H., W.S.D.); Biomedical Informatics and Developmental Biology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (B.J.A.); Experimental Hematology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (T.K.); Hemoshear LLC, Charlottesville, VA (D.M.); and Department of Emergency Medicine, University of Texas Southwestern Medical Center, Dallas (A.B.)
| | - Robert Sturm
- From Hematology/Oncology, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.U., R.S., R.K., R.S., V.B., M.P., R.S.F., V.Y.B.); Vascular Biology Center, Georgia Regents University, Augusta, GA (T.B., S.H., T.C., D.J.F., N.L.W.); Cardiovascular Diseases, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.C., N.B., W.T., D.M.); Department of Nutritional Sciences, College of Allied Health Sciences, University of Cincinnati, OH (D.C., A.P.); Department of Pathology, College of Medicine, University of Cincinnati, OH (D.Y.H., W.S.D.); Biomedical Informatics and Developmental Biology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (B.J.A.); Experimental Hematology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (T.K.); Hemoshear LLC, Charlottesville, VA (D.M.); and Department of Emergency Medicine, University of Texas Southwestern Medical Center, Dallas (A.B.)
| | - Victor Blanco
- From Hematology/Oncology, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.U., R.S., R.K., R.S., V.B., M.P., R.S.F., V.Y.B.); Vascular Biology Center, Georgia Regents University, Augusta, GA (T.B., S.H., T.C., D.J.F., N.L.W.); Cardiovascular Diseases, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.C., N.B., W.T., D.M.); Department of Nutritional Sciences, College of Allied Health Sciences, University of Cincinnati, OH (D.C., A.P.); Department of Pathology, College of Medicine, University of Cincinnati, OH (D.Y.H., W.S.D.); Biomedical Informatics and Developmental Biology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (B.J.A.); Experimental Hematology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (T.K.); Hemoshear LLC, Charlottesville, VA (D.M.); and Department of Emergency Medicine, University of Texas Southwestern Medical Center, Dallas (A.B.)
| | - Mary Palascak
- From Hematology/Oncology, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.U., R.S., R.K., R.S., V.B., M.P., R.S.F., V.Y.B.); Vascular Biology Center, Georgia Regents University, Augusta, GA (T.B., S.H., T.C., D.J.F., N.L.W.); Cardiovascular Diseases, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.C., N.B., W.T., D.M.); Department of Nutritional Sciences, College of Allied Health Sciences, University of Cincinnati, OH (D.C., A.P.); Department of Pathology, College of Medicine, University of Cincinnati, OH (D.Y.H., W.S.D.); Biomedical Informatics and Developmental Biology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (B.J.A.); Experimental Hematology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (T.K.); Hemoshear LLC, Charlottesville, VA (D.M.); and Department of Emergency Medicine, University of Texas Southwestern Medical Center, Dallas (A.B.)
| | - Robert S Franco
- From Hematology/Oncology, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.U., R.S., R.K., R.S., V.B., M.P., R.S.F., V.Y.B.); Vascular Biology Center, Georgia Regents University, Augusta, GA (T.B., S.H., T.C., D.J.F., N.L.W.); Cardiovascular Diseases, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.C., N.B., W.T., D.M.); Department of Nutritional Sciences, College of Allied Health Sciences, University of Cincinnati, OH (D.C., A.P.); Department of Pathology, College of Medicine, University of Cincinnati, OH (D.Y.H., W.S.D.); Biomedical Informatics and Developmental Biology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (B.J.A.); Experimental Hematology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (T.K.); Hemoshear LLC, Charlottesville, VA (D.M.); and Department of Emergency Medicine, University of Texas Southwestern Medical Center, Dallas (A.B.)
| | - Wilson Tong
- From Hematology/Oncology, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.U., R.S., R.K., R.S., V.B., M.P., R.S.F., V.Y.B.); Vascular Biology Center, Georgia Regents University, Augusta, GA (T.B., S.H., T.C., D.J.F., N.L.W.); Cardiovascular Diseases, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.C., N.B., W.T., D.M.); Department of Nutritional Sciences, College of Allied Health Sciences, University of Cincinnati, OH (D.C., A.P.); Department of Pathology, College of Medicine, University of Cincinnati, OH (D.Y.H., W.S.D.); Biomedical Informatics and Developmental Biology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (B.J.A.); Experimental Hematology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (T.K.); Hemoshear LLC, Charlottesville, VA (D.M.); and Department of Emergency Medicine, University of Texas Southwestern Medical Center, Dallas (A.B.)
| | - Tapan Chatterjee
- From Hematology/Oncology, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.U., R.S., R.K., R.S., V.B., M.P., R.S.F., V.Y.B.); Vascular Biology Center, Georgia Regents University, Augusta, GA (T.B., S.H., T.C., D.J.F., N.L.W.); Cardiovascular Diseases, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.C., N.B., W.T., D.M.); Department of Nutritional Sciences, College of Allied Health Sciences, University of Cincinnati, OH (D.C., A.P.); Department of Pathology, College of Medicine, University of Cincinnati, OH (D.Y.H., W.S.D.); Biomedical Informatics and Developmental Biology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (B.J.A.); Experimental Hematology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (T.K.); Hemoshear LLC, Charlottesville, VA (D.M.); and Department of Emergency Medicine, University of Texas Southwestern Medical Center, Dallas (A.B.)
| | - David Y Hui
- From Hematology/Oncology, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.U., R.S., R.K., R.S., V.B., M.P., R.S.F., V.Y.B.); Vascular Biology Center, Georgia Regents University, Augusta, GA (T.B., S.H., T.C., D.J.F., N.L.W.); Cardiovascular Diseases, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.C., N.B., W.T., D.M.); Department of Nutritional Sciences, College of Allied Health Sciences, University of Cincinnati, OH (D.C., A.P.); Department of Pathology, College of Medicine, University of Cincinnati, OH (D.Y.H., W.S.D.); Biomedical Informatics and Developmental Biology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (B.J.A.); Experimental Hematology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (T.K.); Hemoshear LLC, Charlottesville, VA (D.M.); and Department of Emergency Medicine, University of Texas Southwestern Medical Center, Dallas (A.B.)
| | - W Sean Davidson
- From Hematology/Oncology, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.U., R.S., R.K., R.S., V.B., M.P., R.S.F., V.Y.B.); Vascular Biology Center, Georgia Regents University, Augusta, GA (T.B., S.H., T.C., D.J.F., N.L.W.); Cardiovascular Diseases, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.C., N.B., W.T., D.M.); Department of Nutritional Sciences, College of Allied Health Sciences, University of Cincinnati, OH (D.C., A.P.); Department of Pathology, College of Medicine, University of Cincinnati, OH (D.Y.H., W.S.D.); Biomedical Informatics and Developmental Biology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (B.J.A.); Experimental Hematology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (T.K.); Hemoshear LLC, Charlottesville, VA (D.M.); and Department of Emergency Medicine, University of Texas Southwestern Medical Center, Dallas (A.B.)
| | - Bruce J Aronow
- From Hematology/Oncology, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.U., R.S., R.K., R.S., V.B., M.P., R.S.F., V.Y.B.); Vascular Biology Center, Georgia Regents University, Augusta, GA (T.B., S.H., T.C., D.J.F., N.L.W.); Cardiovascular Diseases, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.C., N.B., W.T., D.M.); Department of Nutritional Sciences, College of Allied Health Sciences, University of Cincinnati, OH (D.C., A.P.); Department of Pathology, College of Medicine, University of Cincinnati, OH (D.Y.H., W.S.D.); Biomedical Informatics and Developmental Biology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (B.J.A.); Experimental Hematology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (T.K.); Hemoshear LLC, Charlottesville, VA (D.M.); and Department of Emergency Medicine, University of Texas Southwestern Medical Center, Dallas (A.B.)
| | - Theodosia Kalfa
- From Hematology/Oncology, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.U., R.S., R.K., R.S., V.B., M.P., R.S.F., V.Y.B.); Vascular Biology Center, Georgia Regents University, Augusta, GA (T.B., S.H., T.C., D.J.F., N.L.W.); Cardiovascular Diseases, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.C., N.B., W.T., D.M.); Department of Nutritional Sciences, College of Allied Health Sciences, University of Cincinnati, OH (D.C., A.P.); Department of Pathology, College of Medicine, University of Cincinnati, OH (D.Y.H., W.S.D.); Biomedical Informatics and Developmental Biology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (B.J.A.); Experimental Hematology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (T.K.); Hemoshear LLC, Charlottesville, VA (D.M.); and Department of Emergency Medicine, University of Texas Southwestern Medical Center, Dallas (A.B.)
| | - David Manka
- From Hematology/Oncology, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.U., R.S., R.K., R.S., V.B., M.P., R.S.F., V.Y.B.); Vascular Biology Center, Georgia Regents University, Augusta, GA (T.B., S.H., T.C., D.J.F., N.L.W.); Cardiovascular Diseases, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.C., N.B., W.T., D.M.); Department of Nutritional Sciences, College of Allied Health Sciences, University of Cincinnati, OH (D.C., A.P.); Department of Pathology, College of Medicine, University of Cincinnati, OH (D.Y.H., W.S.D.); Biomedical Informatics and Developmental Biology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (B.J.A.); Experimental Hematology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (T.K.); Hemoshear LLC, Charlottesville, VA (D.M.); and Department of Emergency Medicine, University of Texas Southwestern Medical Center, Dallas (A.B.)
| | - Abigail Peairs
- From Hematology/Oncology, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.U., R.S., R.K., R.S., V.B., M.P., R.S.F., V.Y.B.); Vascular Biology Center, Georgia Regents University, Augusta, GA (T.B., S.H., T.C., D.J.F., N.L.W.); Cardiovascular Diseases, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.C., N.B., W.T., D.M.); Department of Nutritional Sciences, College of Allied Health Sciences, University of Cincinnati, OH (D.C., A.P.); Department of Pathology, College of Medicine, University of Cincinnati, OH (D.Y.H., W.S.D.); Biomedical Informatics and Developmental Biology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (B.J.A.); Experimental Hematology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (T.K.); Hemoshear LLC, Charlottesville, VA (D.M.); and Department of Emergency Medicine, University of Texas Southwestern Medical Center, Dallas (A.B.)
| | - Andra Blomkalns
- From Hematology/Oncology, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.U., R.S., R.K., R.S., V.B., M.P., R.S.F., V.Y.B.); Vascular Biology Center, Georgia Regents University, Augusta, GA (T.B., S.H., T.C., D.J.F., N.L.W.); Cardiovascular Diseases, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.C., N.B., W.T., D.M.); Department of Nutritional Sciences, College of Allied Health Sciences, University of Cincinnati, OH (D.C., A.P.); Department of Pathology, College of Medicine, University of Cincinnati, OH (D.Y.H., W.S.D.); Biomedical Informatics and Developmental Biology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (B.J.A.); Experimental Hematology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (T.K.); Hemoshear LLC, Charlottesville, VA (D.M.); and Department of Emergency Medicine, University of Texas Southwestern Medical Center, Dallas (A.B.)
| | - David J Fulton
- From Hematology/Oncology, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.U., R.S., R.K., R.S., V.B., M.P., R.S.F., V.Y.B.); Vascular Biology Center, Georgia Regents University, Augusta, GA (T.B., S.H., T.C., D.J.F., N.L.W.); Cardiovascular Diseases, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.C., N.B., W.T., D.M.); Department of Nutritional Sciences, College of Allied Health Sciences, University of Cincinnati, OH (D.C., A.P.); Department of Pathology, College of Medicine, University of Cincinnati, OH (D.Y.H., W.S.D.); Biomedical Informatics and Developmental Biology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (B.J.A.); Experimental Hematology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (T.K.); Hemoshear LLC, Charlottesville, VA (D.M.); and Department of Emergency Medicine, University of Texas Southwestern Medical Center, Dallas (A.B.)
| | - Julia E Brittain
- From Hematology/Oncology, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.U., R.S., R.K., R.S., V.B., M.P., R.S.F., V.Y.B.); Vascular Biology Center, Georgia Regents University, Augusta, GA (T.B., S.H., T.C., D.J.F., N.L.W.); Cardiovascular Diseases, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.C., N.B., W.T., D.M.); Department of Nutritional Sciences, College of Allied Health Sciences, University of Cincinnati, OH (D.C., A.P.); Department of Pathology, College of Medicine, University of Cincinnati, OH (D.Y.H., W.S.D.); Biomedical Informatics and Developmental Biology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (B.J.A.); Experimental Hematology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (T.K.); Hemoshear LLC, Charlottesville, VA (D.M.); and Department of Emergency Medicine, University of Texas Southwestern Medical Center, Dallas (A.B.)
| | - Neal L Weintraub
- From Hematology/Oncology, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.U., R.S., R.K., R.S., V.B., M.P., R.S.F., V.Y.B.); Vascular Biology Center, Georgia Regents University, Augusta, GA (T.B., S.H., T.C., D.J.F., N.L.W.); Cardiovascular Diseases, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.C., N.B., W.T., D.M.); Department of Nutritional Sciences, College of Allied Health Sciences, University of Cincinnati, OH (D.C., A.P.); Department of Pathology, College of Medicine, University of Cincinnati, OH (D.Y.H., W.S.D.); Biomedical Informatics and Developmental Biology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (B.J.A.); Experimental Hematology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (T.K.); Hemoshear LLC, Charlottesville, VA (D.M.); and Department of Emergency Medicine, University of Texas Southwestern Medical Center, Dallas (A.B.)
| | - Vladimir Y Bogdanov
- From Hematology/Oncology, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.U., R.S., R.K., R.S., V.B., M.P., R.S.F., V.Y.B.); Vascular Biology Center, Georgia Regents University, Augusta, GA (T.B., S.H., T.C., D.J.F., N.L.W.); Cardiovascular Diseases, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH (D.C., N.B., W.T., D.M.); Department of Nutritional Sciences, College of Allied Health Sciences, University of Cincinnati, OH (D.C., A.P.); Department of Pathology, College of Medicine, University of Cincinnati, OH (D.Y.H., W.S.D.); Biomedical Informatics and Developmental Biology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (B.J.A.); Experimental Hematology / Department of Pediatrics, College of Medicine, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, OH (T.K.); Hemoshear LLC, Charlottesville, VA (D.M.); and Department of Emergency Medicine, University of Texas Southwestern Medical Center, Dallas (A.B.).
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Mechanisms linking red blood cell disorders and cardiovascular diseases. BIOMED RESEARCH INTERNATIONAL 2015; 2015:682054. [PMID: 25710019 PMCID: PMC4331396 DOI: 10.1155/2015/682054] [Citation(s) in RCA: 97] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/27/2014] [Revised: 11/14/2014] [Accepted: 11/23/2014] [Indexed: 01/07/2023]
Abstract
The present paper aims to review the main pathophysiological links between red blood cell disorders and cardiovascular diseases, provides a brief description of the latest studies in this area, and considers implications for clinical practice and therapy. Anemia is associated with a special risk in proatherosclerotic conditions and heart disease and became a new therapeutic target. Guidelines must be updated for the management of patients with red blood cell disorders and cardiovascular diseases, and targets for hemoglobin level should be established. Risk scores in several cardiovascular diseases should include red blood cell count and RDW. Complete blood count and hemorheological parameters represent useful, inexpensive, widely available tools for the management and prognosis of patients with coronary heart disease, heart failure, hypertension, arrhythmias, and stroke. Hypoxia and iron accumulation cause the most important cardiovascular effects of sickle cell disease and thalassemia. Patients with congenital chronic hemolytic anemia undergoing splenectomy should be monitored, considering thromboembolic and cardiovascular risk.
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27
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Piroxicam and c-phycocyanin prevent colon carcinogenesis by inhibition of membrane fluidity and canonical Wnt/β-catenin signaling while up-regulating ligand dependent transcription factor PPARγ. Biomed Pharmacother 2014; 68:537-50. [DOI: 10.1016/j.biopha.2014.03.007] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2014] [Accepted: 03/04/2014] [Indexed: 12/12/2022] Open
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García JJ, López-Pingarrón L, Almeida-Souza P, Tres A, Escudero P, García-Gil FA, Tan DX, Reiter RJ, Ramírez JM, Bernal-Pérez M. Protective effects of melatonin in reducing oxidative stress and in preserving the fluidity of biological membranes: a review. J Pineal Res 2014; 56:225-37. [PMID: 24571249 DOI: 10.1111/jpi.12128] [Citation(s) in RCA: 336] [Impact Index Per Article: 30.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2014] [Accepted: 02/20/2014] [Indexed: 12/14/2022]
Abstract
Free radicals generated within subcellular compartments damage macromolecules which lead to severe structural changes and functional alterations of cellular organelles. A manifestation of free radical injury to biological membranes is the process of lipid peroxidation, an autooxidative chain reaction in which polyunsaturated fatty acids in the membrane are the substrate. There is considerable evidence that damage to polyunsaturated fatty acids tends to reduce membrane fluidity. However, adequate levels of fluidity are essential for the proper functioning of biological membranes. Thus, there is considerable interest in antioxidant molecules which are able to stabilize membranes because of their protective effects against lipid peroxidation. Melatonin is an indoleamine that modulates a wide variety of endocrine, neural and immune functions. Over the last two decades, intensive research has proven this molecule, as well as its metabolites, to possess substantial antioxidant activity. In addition to their ability to scavenge several reactive oxygen and nitrogen species, melatonin increases the activity of the glutathione redox enzymes, that is, glutathione peroxidase and reductase, as well as other antioxidant enzymes. These beneficial effects of melatonin are more significant because of its small molecular size and its amphipathic behaviour, which facilitates ease of melatonin penetration into every subcellular compartment. In the present work, we review the current information related to the beneficial effects of melatonin in maintaining the fluidity of biological membranes against free radical attack, and further, we discuss its implications for ageing and disease.
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Affiliation(s)
- Joaquín J García
- Department of Pharmacology and Physiology, University of Zaragoza, Zaragoza, Spain
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29
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Mascarenhas Netto RDC, Fabbri C, de Freitas MV, Bernardino Neto M, Garrote-Filho MS, Lacerda MVG, Lima ES, Penha-Silva N. Influence of Plasmodium vivax malaria on the relations between the osmotic stability of human erythrocyte membrane and hematological and biochemical variables. Parasitol Res 2014; 113:863-74. [PMID: 24322291 DOI: 10.1007/s00436-013-3717-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2013] [Accepted: 11/21/2013] [Indexed: 01/28/2023]
Abstract
This study evaluated the influence of infection by Plasmodium vivax on the relations between hematological and biochemical variables and the osmotic stability of the erythrocyte membrane in a Brazilian Amazon population. A total of 72 patients with P. vivax malaria were included in the study and invited to return after 14 days, post-treatment with chloroquine and primaquine, for clinical and laboratorial reevaluations. The osmotic stability of the erythrocyte membrane was analyzed by nonlinear regression of the dependency of the absorbance of hemoglobin, released with hemolysis, as a function of the salt concentration, and it was represented by the inverse of the salt concentration at the midpoint of the curve (1/H 50) and by the variation of salt concentration, which promotes lysis (dX). Bivariate and multivariate methods were used in the analysis of the results. Prior to treatment of the disease, the erythrocytes showed greater stability, probably due to the natural selection of young and also more stable erythrocytes. The bivariate analysis showed that 1/H 50 was positively correlated with red cell distribution width (RDW), urea, triglycerides, and very low-density lipoprotein (VLDL)-cholesterol, but negatively associated with albumin, HDL-cholesterol, and indirect bilirubin, while dX was negatively associated with the mean corpuscular hemoglobin concentration. These associations were confirmed by canonical correlation analysis. Stepwise multiple linear regression showed that albumin, urea, triglycerides, and VLDL-cholesterol are the variables with the highest abilities of predicting erythrocyte stability. The bivariate analysis also showed that the hematological index RDW was related to elevated levels of bilirubin and decreased levels of albumin and urea, associated with liver damage resulting from malaria.
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30
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Sengupta A, Ghosh M. Effect of Sterol Esters on Lipid Composition and Antioxidant Status of Erythrocyte Membrane of Hypercholesterolemic Rats. J Oleo Sci 2014; 63:439-47. [DOI: 10.5650/jos.ess13211] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
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31
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de Freitas MV, Marquez-Bernardes LF, de Arvelos LR, Paraíso LF, Gonçalves e Oliveira AFM, Mascarenhas Netto RDC, Neto MB, Garrote-Filho MS, de Souza PCA, Penha-Silva N. Influence of age on the correlations of hematological and biochemical variables with the stability of erythrocyte membrane in relation to sodium dodecyl sulfate. Hematology 2013; 19:424-30. [DOI: 10.1179/1607845413y.0000000145] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022] Open
Affiliation(s)
- Mariana V. de Freitas
- Institute of Genetics and BiochemistryFederal University of Uberlândia, Uberlândia, MG, Brazil
| | | | - Letícia R. de Arvelos
- Institute of Genetics and BiochemistryFederal University of Uberlândia, Uberlândia, MG, Brazil
| | - Lara F. Paraíso
- Institute of Genetics and BiochemistryFederal University of Uberlândia, Uberlândia, MG, Brazil
| | | | | | - Morun Bernardino Neto
- Institute of Genetics and BiochemistryFederal University of Uberlândia, Uberlândia, MG, Brazil
| | - Mario S. Garrote-Filho
- Institute of Genetics and BiochemistryFederal University of Uberlândia, Uberlândia, MG, Brazil
| | - Paulo César A. de Souza
- Institute of Genetics and BiochemistryFederal University of Uberlândia, Uberlândia, MG, Brazil
| | - Nilson Penha-Silva
- Institute of Genetics and BiochemistryFederal University of Uberlândia, Uberlândia, MG, Brazil
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32
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Fessler MB, Rose K, Zhang Y, Jaramillo R, Zeldin DC. Relationship between serum cholesterol and indices of erythrocytes and platelets in the US population. J Lipid Res 2013; 54:3177-88. [PMID: 23999863 DOI: 10.1194/jlr.p037614] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
Whereas dyslipidemia has been associated with leukocytosis, the relationship between serum cholesterol and other hematopoietic lineages is poorly defined. Erythrocytes and platelets, anucleate cells relegated to nonspecific diffusional exchange of cholesterol with serum, have been proposed to have a distinct relationship to cholesterol from leukocytes. We examined the relationship between serum cholesterol and circulating erythrocyte/platelet indices in 4,469 adult participants of the National Health and Nutrition Examination Survey (NHANES) 2005-2006. In linear regression analyses, serum non-high density lipoprotein-cholesterol (non-HDL-C) was positively associated with mean erythrocyte number, hematocrit, hemoglobin concentration, platelet count, and platelet crit independently of age, gender, race/ethnicity, smoking, body mass index, serum folate, and C-reactive protein. The magnitude of the relationship was most marked for platelets, with lowest versus highest non-HDL-C quartile subjects having geometric mean platelet counts of 258,000/μl versus 281,000/μl, respectively (adjusted model, P < 0.001 for trend). These associations persisted in a sensitivity analysis excluding several conditions that affect erythrocyte/platelet and/or serum cholesterol levels, and were also noted in an independent analysis of 5,318 participants from NHANES 2007-2008. As non-HDL-C, erythrocytes, and platelets all impact cardiovascular disease risk, there is a need for advancing understanding of the underlying interactions that govern levels of these three blood components.
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Affiliation(s)
- Michael B Fessler
- Laboratory of Respiratory Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709
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Wu H, Ding EL, Toledo ET, Campos H, Baylin A, Hu FB, Sun Q. A novel fatty acid lipophilic index and risk of CHD in US men: the health professionals follow-up study. Br J Nutr 2013; 110:466-74. [PMID: 23298409 PMCID: PMC3723798 DOI: 10.1017/s0007114512005272] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Few epidemiological studies have examined the association between an overall fatty acid (FA) profile and CHD risk. The aim of the present study was to examine a novel index that summarises individual FA levels based on FA affinity and fluidity in relation to CHD risk in men. In a prospective nested case–control study, FA in plasma and erythrocytes were measured in 459 CHD cases and 879 matched controls. Lipophilic index (LI) was computed by summing the products between FA levels and melting point of each FA to reflect the overall FA lipophilicity. Among controls, higher plasma LI was significantly correlated with adverse profiles of blood lipids, inflammatory markers and adiponectin. After multivariate adjustment for age, smoking, BMI and other CHD risk factors, plasma LI was significantly associated with an increased risk of CHD: the relative risk was 1·61 (95% CI 1·03, 2·53; P for trend¼0·04) comparing extreme quintiles. This association was attenuated to 1·21 (95% CI 0·48, 3·09; P for trend¼0·77) after adjusting for plasma levels of total trans-FA, long-chain n-3 FA and polyunsaturated:saturated fat ratio. Erythrocyte LI was not significantly associated with CHD risk. The present data indicate that a novel LI is associated with an adverse profile of cardiovascular risk markers and increased risk of CHD in men; its usefulness as a complement of individual FA in assessing disease risk needs to be elucidated in future studies.
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Affiliation(s)
- Hongyu Wu
- Department of Nutrition, Harvard School of Public Health, Boston, MA
| | - Eric L. Ding
- Department of Nutrition, Harvard School of Public Health, Boston, MA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
| | - Estefanía T. Toledo
- Department of Nutrition, Harvard School of Public Health, Boston, MA
- Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain
| | - Hannia Campos
- Department of Nutrition, Harvard School of Public Health, Boston, MA
| | - Ana Baylin
- Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI
| | - Frank B. Hu
- Department of Nutrition, Harvard School of Public Health, Boston, MA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
- Department of Epidemiology, Harvard School of Public Health, Boston, MA
| | - Qi Sun
- Department of Nutrition, Harvard School of Public Health, Boston, MA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
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Tsuda K. Chronic kidney disease predicts impaired membrane microviscosity of red blood cells in hypertensive and normotensive subjects. Int Heart J 2013; 54:154-9. [PMID: 23774239 DOI: 10.1536/ihj.54.154] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Current evidence indicates that abnormalities in physical properties of the cell membranes may be strongly linked to hypertension and other circulatory disorders. Recent studies have shown that chronic kidney disease (CKD) might be a risk factor for cardiovascular and cerebrovascular outcomes. The purpose of the present study was to examine the possible relationship between kidney function and membrane fluidity (a reciprocal value of membrane microviscosity) of red blood cells (RBCs) in hypertensive and normotensive subjects using an electron spin resonance (ESR) and spin-labeling method. The order parameter (S) for the ESR spin-label agent (5-nitroxide stearate) in RBC membranes was significantly higher in hypertensive subjects than in normotensive subjects, indicating that membrane fluidity was decreased in hypertension. The order parameter (S) of RBCs was inversely correlated with estimated glomerular filtration rate (eGFR), suggesting that a decreased eGFR value might be associated with reduced membrane fluidity of RBCs. Multivariate regression analysis also demonstrated that, after adjustment for general risk factors, eGFR might be a significant predictor of membrane fluidity of RBCs. The reduced levels of both membrane fluidity of RBCs and eGFR were associated with increased plasma 8-iso-prostaglandin F2α (an index of oxidative stress) and decreased plasma nitric oxide (NO)-metabolites, suggesting that kidney function could be a determinant of membrane microviscosity of RBCs, at least in part, via oxidative stress- and NO-dependent mechanisms. The ESR study suggests that CKD might have a close correlation with impaired rheologic behavior of RBCs and microcirculatory disorders in hypertensive subjects.
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Affiliation(s)
- Kazushi Tsuda
- Cardiovascular and Metabolic Research Center, Kansai University of Health Sciences, Osaka, Japan
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35
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Golfetto O, Hinde E, Gratton E. Laurdan fluorescence lifetime discriminates cholesterol content from changes in fluidity in living cell membranes. Biophys J 2013; 104:1238-47. [PMID: 23528083 DOI: 10.1016/j.bpj.2012.12.057] [Citation(s) in RCA: 118] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2012] [Revised: 12/16/2012] [Accepted: 12/21/2012] [Indexed: 01/17/2023] Open
Abstract
Detection of the fluorescent properties of Laurdan has been proven to be an efficient tool to investigate membrane packing and ordered lipid phases in model membranes and living cells. Traditionally the spectral shift of Laurdan's emission from blue in the ordered lipid phase of the membrane (more rigid) toward green in the disordered lipid phase (more fluid) is quantified by the generalized polarization function. Here, we investigate the fluorescence lifetime of Laurdan at two different emission wavelengths and find that when the dipolar relaxation of Laurdan's emission is spectrally isolated, analysis of the fluorescence decay can distinguish changes in membrane fluidity from changes in cholesterol content. Using the phasor representation to analyze changes in Laurdan's fluorescence lifetime we obtain two different phasor trajectories for changes in polarity versus changes in cholesterol content. This gives us the ability to resolve in vivo membranes with different properties such as water content and cholesterol content and thus perform a more comprehensive analysis of cell membrane heterogeneity. We demonstrate this analysis in NIH3T3 cells using Laurdan as a biosensor to monitor changes in the membrane water content during cell migration.
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Affiliation(s)
- Ottavia Golfetto
- Laboratory for Fluorescence Dynamics, Department of Biomedical Engineering, University of California, Irvine, CA, USA
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36
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de Arvelos LR, Rocha VCA, Felix GP, da Cunha CC, Bernardino Neto M, da Silva Garrote Filho M, de Fátima Pinheiro C, Resende ES, Penha-Silva N. Bivariate and multivariate analyses of the influence of blood variables of patients submitted to Roux-en-Y gastric bypass on the stability of erythrocyte membrane against the chaotropic action of ethanol. J Membr Biol 2013; 246:231-42. [PMID: 23344659 DOI: 10.1007/s00232-013-9524-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2012] [Accepted: 01/01/2013] [Indexed: 11/26/2022]
Abstract
The stability of the erythrocyte membrane, which is essential for the maintenance of cell functions, occurs in a critical region of fluidity, which depends largely on its composition and the composition and characteristics of the medium. As the composition of the erythrocyte membrane is influenced by several blood variables, the stability of the erythrocyte membrane must have relations with them. The present study aimed to evaluate, by bivariate and multivariate statistical analyses, the correlations and causal relationships between hematologic and biochemical variables and the stability of the erythrocyte membrane against the chaotropic action of ethanol. The validity of this type of analysis depends on the homogeneity of the population and on the variability of the studied parameters, conditions that can be filled by patients who undergo bariatric surgery by the technique of Roux-en-Y gastric bypass since they will suffer feeding restrictions that have great impact on their blood composition. Pathway analysis revealed that an increase in hemoglobin leads to decreased stability of the cell, probably through a process mediated by an increase in mean corpuscular volume. Furthermore, an increase in the mean corpuscular hemoglobin (MCH) leads to an increase in erythrocyte membrane stability, probably because higher values of MCH are associated with smaller quantities of red blood cells and a larger contact area between the cell membrane and ethanol present in the medium.
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Affiliation(s)
- Leticia Ramos de Arvelos
- Instituto de Genética e Bioquímica, Universidade Federal de Uberlândia, Av. Pará, 1720, Uberlândia, MG 38400-902, Brazil
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37
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Ability of S-Adenosyl-L-Methionine to Ameliorate Lipoprotein-Induced Membrane Lipid Abnormalities and Cellular Dysfunctions in Human Liver Disease. ACTA ACUST UNITED AC 2012. [DOI: 10.1007/bf03258361] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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38
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Yurt S, Erman H, Korkmaz GG, Kosar AF, Uysal P, Gelisgen R, Simsek G, Uzun H. The role of feed regulating peptides on weight loss in patients with pulmonary tuberculosis. Clin Biochem 2012; 46:40-4. [PMID: 23000316 DOI: 10.1016/j.clinbiochem.2012.09.008] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2012] [Revised: 09/10/2012] [Accepted: 09/11/2012] [Indexed: 12/19/2022]
Abstract
PURPOSE Malnutrition is a prominent feature of tuberculosis (TB). The aim of our study was to explore the function of plasma regulatory proteins in pulmonary TB and to investigate the relationship between these parameters and loss of body weight. METHODS Plasma levels of fasting insulin, leptin, ghrelin, adiponectin and orexin-A were measured in 23 pulmonary TB patients, 39 patients with pulmonary sarcoidosis, 22 patients with different diffuse interstitial lung diseases and 21 healthy patients serving as controls. RESULT Plasma leptin (p<0.001) and orexin-A (p<0.01) levels were significantly decreased in TB patients compared with those of the other study subjects. TB patients also had higher levels of plasma ghrelin compared with those of the other study subjects, while sarcoidosis patients had higher plasma adiponectin levels than the other study subjects. Glucose levels were similar in all groups, yet, insulin and Homeostasis Model of Assessment-Insulin Resistance (HOMA-IR) levels were significantly higher in the TB group compared to the other study groups. There was no correlation between leptin, ghrelin, adiponectin and orexin-A and other parameters. CONCLUSIONS These data suggest that leptin and orexin-A levels have effects on weight loss in patients with pulmonary tuberculosis. Particularly, leptin may play a role in the early immune response to pulmonary TB and prolonged inflammation may further suppress leptin production. Measurement of HOMA-IR can indeed be used as a marker for the risk of activated TB. Further clinical studies are needed to better understand the role of feed regulating proteins in pulmonary tuberculosis.
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Affiliation(s)
- S Yurt
- Yedikule Chest Disease and Chest Surgery Education and Research Hospital, Istanbul, Turkey.
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39
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Tavolari S, Munarini A, Storci G, Laufer S, Chieco P, Guarnieri T. The decrease of cell membrane fluidity by the non-steroidal anti-inflammatory drug Licofelone inhibits epidermal growth factor receptor signalling and triggers apoptosis in HCA-7 colon cancer cells. Cancer Lett 2012; 321:187-94. [DOI: 10.1016/j.canlet.2012.02.003] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2011] [Revised: 12/31/2011] [Accepted: 02/06/2012] [Indexed: 10/14/2022]
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40
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Associations between High-Sensitivity C-Reactive Protein and Membrane Fluidity of Red Blood Cells in Hypertensive Elderly Men: An Electron Spin Resonance Study. Int J Hypertens 2012; 2012:292803. [PMID: 22518282 PMCID: PMC3296171 DOI: 10.1155/2012/292803] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2011] [Accepted: 10/13/2011] [Indexed: 11/27/2022] Open
Abstract
Recent evidence indicates that high-sensitivity C-reactive protein (hs-CRP), an acute phase of an inflammatory marker, might be associated with atherosclerosis, hypertension, and other cardiovascular diseases. The present study was performed to assess the possible link between plasma hs-CRP and membrane fluidity (a reciprocal value of membrane microviscosity) in hypertensive elderly men. We measured the membrane fluidity of red blood cells (RBCs) in hypertensive and normotensive elderly men using an electron spin resonance and spin-labeling method. Membrane fluidity of RBCs was decreased in hypertensive elderly men compared with normotensive elderly men. Plasma hs-CRP levels were significantly higher in hypertensive elderly men than in normotensive elderly men. In contrast, plasma nitric-oxide- (NO-) metabolite levels were lower in hypertensive elderly men than in normotensive elderly men. The reduced membrane fluidity of RBCs was associated with increased plasma hs-CRP and decreased plasma NO-metabolite levels. In a multivariate regression analysis, plasma hs-CRP was an independent determinant of membrane fluidity of RBCs after adjustment for general risk factors. The results suggest that CRP might have a close correlation with the rheologic behavior of RBCs and the microcirculation and would contribute, at least in part, to the circulatory dysfunction and vascular complications in hypertensive elderly men.
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41
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Influence of Phospholipid Species on Membrane Fluidity: A Meta-analysis for a Novel Phospholipid Fluidity Index. J Membr Biol 2011; 244:97-103. [DOI: 10.1007/s00232-011-9401-7] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2011] [Accepted: 10/15/2011] [Indexed: 01/06/2023]
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42
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Sengupta A, Ghosh M. Integrity of erythrocytes of hypercholesterolemic and normocholesterolemic rats during ingestion of different structured lipids. Eur J Nutr 2010; 50:411-9. [DOI: 10.1007/s00394-010-0150-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2010] [Accepted: 11/15/2010] [Indexed: 10/18/2022]
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43
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Pasini EM, Mann M, Thomas AW. Red blood cell proteomics. Transfus Clin Biol 2010; 17:151-64. [PMID: 20655788 DOI: 10.1016/j.tracli.2010.05.010] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2010] [Accepted: 05/21/2010] [Indexed: 12/23/2022]
Abstract
Since its discovery in the 17th century, the red blood cell, recognized in time as the critical cell component for survival, has been the focus of much attention. Its unique role in gas exchange (oxygen/CO(2) transport) and its distinct characteristics (absence of nucleus; biconcave cell shape) together with an - in essence - unlimited supply lead to extensive targeted biochemical, molecular and structural studies. A quick PubMed query with the word "erythrocyte" results in 198 013 scientific articles of which 162 are red blood cell proteomics studies, indicating that this new technique has been only recently applied to the red blood cell and related fields. Standard and comparative proteomics have been widely used to study different blood components. A growing body of proteomics literature has since developed, which deals with the characterization of red blood cells in health and disease. The possibility offered by proteomics to obtain a global snapshot of the whole red blood cell protein make-up, has provided unique insights to many fields including transfusion medicine, anaemia studies, intra-red blood cell parasite biology and translational research. While the contribution of proteomics is beyond doubt, a full red blood cell understanding will ultimately require, in addition to proteomics, lipidomics, glycomics, interactomics and study of post-translational modifications. In this review we will briefly discuss the methodology and limitations of proteomics, the contribution it made to the understanding of the erythrocyte and the advances in red blood cell-related fields brought about by comparative proteomics.
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Affiliation(s)
- E M Pasini
- Biomedical Primate Research Centre, Lange Kleiweg 139, 2288 GJ Rijswijk, The Netherlands
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44
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Yang JG, Yu HN, Sun SL, Zhang LC, He GQ, Das UN, Ruan H, Shen SR. Epigallocatechin-3-gallate affects the growth of LNCaP cells via membrane fluidity and distribution of cellular zinc. J Zhejiang Univ Sci B 2009; 10:411-21. [PMID: 19489106 DOI: 10.1631/jzus.b0820400] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
OBJECTIVE To evaluate effects of epigallocatechin-3-gallate (EGCG) on the viability, membrane properties, and zinc distribution, with and without the presence of Zn(2+), in human prostate carcinoma LNCaP cells. METHODS We examined changes in cellular morphology and membrane fluidity of LNCaP cells, distribution of cellular zinc, and the incorporated portion of EGCG after treatments with EGCG, Zn(2+), and EGCG+Zn(2+). RESULTS We observed an alteration in cellular morphology and a decrease in membrane fluidity of LNCaP cells after treatment with EGCG or Zn(2+). The proportion of EGCG incorporated into liposomes treated with the mixture of EGCG and Zn(2+) at the ratio of 1:1 was 90.57%, which was significantly higher than that treated with EGCG alone (30.33%). Electron spin resonance (ESR) studies and determination of fatty acids showed that the effects of EGCG on the membrane fluidity of LNCaP were decreased by Zn(2+). EGCG accelerated the accumulation of zinc in the mitochondria and cytosol as observed by atomic absorption spectrometer. CONCLUSION These results show that EGCG interacted with cell membrane, decreased the membrane fluidity of LNCaP cells, and accelerated zinc accumulation in the mitochondria and cytosol, which could be the mechanism by which EGCG inhibits proliferation of LNCaP cells. In addition, high concentrations of Zn(2+) could attenuate the actions elicited by EGCG.
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Affiliation(s)
- Jun-guo Yang
- Department of Food Science and Nutrition, Zhejiang University, Hangzhou 310029, China
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45
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Pasini EM, Lutz HU, Mann M, Thomas AW. Red blood cell (RBC) membrane proteomics--Part I: Proteomics and RBC physiology. J Proteomics 2009; 73:403-20. [PMID: 19540949 DOI: 10.1016/j.jprot.2009.06.005] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2009] [Revised: 05/29/2009] [Accepted: 06/04/2009] [Indexed: 10/20/2022]
Abstract
Membrane proteomics is concerned with accurately and sensitively identifying molecules involved in cell compartmentalisation, including those controlling the interface between the cell and the outside world. The high lipid content of the environment in which these proteins are found often causes a particular set of problems that must be overcome when isolating the required material before effective HPLC-MS approaches can be performed. The membrane is an unusually dynamic cellular structure since it interacts with an ever changing environment. A full understanding of this critical cell component will ultimately require, in addition to proteomics, lipidomics, glycomics, interactomics and study of post-translational modifications. Devoid of nucleus and organelles in mammalian species other than camelids, and constantly in motion in the blood stream, red blood cells (RBCs) are the sole mammalian oxygen transporter. The fact that mature mammalian RBCs have no internal membrane-bound organelles, somewhat simplifies proteomics analysis of the plasma membrane and the fact that it has no nucleus disqualifies microarray based methods. Proteomics has the potential to provide a better understanding of this critical interface, and thereby assist in identifying new approaches to diseases.
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Affiliation(s)
- Erica M Pasini
- Biomedical Primate Research Centre, Lange Kleiweg 139, 2288 GJ Rijswijk, The Netherlands
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46
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47
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Evaluation of antioxidant capacity of Allium ursinum L. volatile oil and its effect on membrane fluidity. Food Chem 2008. [DOI: 10.1016/j.foodchem.2007.10.017] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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48
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Kuwai T, Hayashi J. Nitric oxide pathway activation and impaired red blood cell deformability with hypercholesterolemia. J Atheroscler Thromb 2007; 13:286-94. [PMID: 17192693 DOI: 10.5551/jat.13.286] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
Abstract
The pathophysiological effects of the activation or inhibition of the nitric oxide (NO)-mediated pathway on the deformability of red blood cells (RBC) were evaluated in the presence of hypercholesterolemia induced in rabbits fed a cholesterol-rich diet. RBC deformability was assessed using a microchannel array flow analyzer system. The maximum passage time (MPT) by flowing a suspension of RBC through the microchannels was used as an index of RBC deformability. During cholesterol feeding for 12 weeks, MPT gradually increased with no significant elevation in the serum asymmetric dimethylarginine (ADMA) and arginine/ADMA ratio. The reduction in RBC deformability associated with hypercholesterolemia was significantly improved during incubation with each of three different NO pathway activators: a NO donor, 8-bromo-cyclic GMP, and arginine; however, no additional reduction was observed with ADMA administration. The inhibition of NO synthase due to ADMA caused a significant reduction in the deformability of normal RBC, which was reversed with NO pathway activation. These results suggest that impaired RBC deformability may be associated with a dysfunction in the NO pathway that is partially dependent upon the accumulation of ADMA in RBC, and exogenous NO pathway activators may improve the microcirculation by restoring RBC deformability in the presence of hypercholesterolemia.
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Affiliation(s)
- Taro Kuwai
- Department of General Medicine, School of Medicine, Kyorin University, Tokyo, Japan
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49
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Nikolić M, Stanić D, Baricević I, Jones DR, Nedić O, Niketić V. Efflux of cholesterol and phospholipids derived from the haemoglobin-lipid adduct in human red blood cells into plasma. Clin Biochem 2006; 40:305-9. [PMID: 17291471 DOI: 10.1016/j.clinbiochem.2006.11.005] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2006] [Revised: 10/17/2006] [Accepted: 11/05/2006] [Indexed: 11/29/2022]
Abstract
OBJECTIVE The interior of red blood cells (RBCs) contains a variable amount of cholesterol and phospholipids bound to haemoglobin (Hb). This current study was devised to determine if this pool of lipids (termed Hb-Ch) was available for exchange with plasma lipoproteins. DESIGN AND METHODS We studied the in vitro efflux of lipids from human RBCs into fasting plasma in men with either low (control group) or high Hb-Ch (study group). RESULTS When plasma was incubated with a two-fold excess of autologous RBCs the plasma cholesterol level increased due to a decrease in the level of cholesterol from the RBC membrane (in the control group) and due to a decrease in the level of cholesterol both from the RBC membrane and the Hb-Ch fraction (in the study group). The loss of Hb-Ch-derived phospholipids during lipid efflux was roughly equal to that of Hb-Ch-derived cholesterol. The loss of RBC cholesterol into plasma high-density lipoproteins (HDL) was more pronounced in our study group and correlated with the loss of cholesterol from Hb-Ch. CONCLUSION The Hb-Ch adduct significantly contributes to the lipid efflux from RBCs into plasma. The majority of cholesterol released from Hb-Ch appears in the plasma HDL fraction suggesting that Hb-Ch may play a role in reverse cholesterol transport in vivo.
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Affiliation(s)
- Milan Nikolić
- Faculty of Chemistry, University of Belgrade, Studentski trg 16, P.O. Box 158, 11001 Belgrade, Serbia.
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50
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Deniz O, Gumus S, Yaman H, Ciftci F, Ors F, Cakir E, Tozkoparan E, Bilgic H, Ekiz K. Serum total cholesterol, HDL-C and LDL-C concentrations significantly correlate with the radiological extent of disease and the degree of smear positivity in patients with pulmonary tuberculosis. Clin Biochem 2006; 40:162-6. [PMID: 17217941 DOI: 10.1016/j.clinbiochem.2006.10.015] [Citation(s) in RCA: 67] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2006] [Revised: 09/19/2006] [Accepted: 10/03/2006] [Indexed: 11/23/2022]
Abstract
BACKGROUND Low serum total cholesterol (TC) concentrations in patients with pulmonary tuberculosis (PTB) have been demonstrated. It was shown that a cholesterol-rich diet might accelerate the sterilization rate of sputum cultures in PTB patients. It is known that smear positivity might be related to the radiological extent of disease (RED) in PTB patients. OBJECTIVE We hypothesized that there might be a relationship between initial serum TC concentrations; the degree of RED (DRED) and the degree of smear positivity (DSP) in PTB patients. METHOD Eighty-three PTB patients and 39 healthy controls were included in the study. Serum TC, TG, HDL-C, VLDL-C and LDL-C concentrations were determined in all subjects. PTB patients were classified for their chest X-ray findings as minimal/mild, moderate and advanced. Correlations between serum lipid concentrations, DRED and DSP (0, 1+, 2+, 3+, 4+) were investigated. PTB patients and controls were also compared for serum lipid concentrations. RESULTS Significant differences between PTB patients and controls were detected for serum TC, HDL-C and LDL-C concentrations. On stepwise logistic regression analysis, DRED was found as one of the significant independent predictors of serum TC levels. We also found significant correlations between DRED and serum HDL-C concentrations (r=-0.60, p=0.0001) and between DRED and serum LDL-C concentrations (r=-0.28, p=0.011). There were also significant correlations between DSP and serum lipid concentrations. CONCLUSION Our study suggests that serum TC, HDL-C and LDL-C concentrations are generally lower in patients with PTB than those in healthy controls. In addition, changes in these parameters might be related to DRED and DSP in PTB patients.
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Affiliation(s)
- Omer Deniz
- Department of Pulmonary Medicine and Tuberculosis, Gulhane Military Medical Academy, Ankara, Turkey.
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