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Gwozdzinski L, Pieniazek A, Gwozdzinski K. The Roles of Oxidative Stress and Red Blood Cells in the Pathology of the Varicose Vein. Int J Mol Sci 2024; 25:13400. [PMID: 39769165 PMCID: PMC11678264 DOI: 10.3390/ijms252413400] [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: 11/02/2024] [Revised: 11/25/2024] [Accepted: 12/10/2024] [Indexed: 01/11/2025] Open
Abstract
This review discusses sources of reactive oxygen species, enzymatic antioxidant systems, and low molecular weight antioxidants. We present the pathology of varicose veins (VVs), including factors such as hypoxia, inflammation, dysfunctional endothelial cells, risk factors in varicose veins, the role of RBCs in venous thrombus formation, the influence of reactive oxygen species (ROS) and RBCs on VV pathology, and the role of hemoglobin in the damage of particles and macromolecules in VVs. This review discusses the production of ROS, enzymatic and nonenzymatic antioxidants, the pathogenesis of varicose veins as a pathology based on hypoxia, inflammation, and oxidative stress, as well as the participation of red blood cells in the pathology of varicose veins.
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Affiliation(s)
- Lukasz Gwozdzinski
- Department of Pharmacology and Toxicology, Medical University of Lodz, 90-752 Lodz, Poland
| | - Anna Pieniazek
- Department of Oncobiology and Epigenetics, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland; (A.P.); (K.G.)
| | - Krzysztof Gwozdzinski
- Department of Oncobiology and Epigenetics, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland; (A.P.); (K.G.)
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Sheet PS, Lautner G, Meyerhoff ME, Schwendeman SP. Mechanistic analysis of the photolytic decomposition of solid-state S-nitroso-N-acetylpenicillamine. Nitric Oxide 2024; 142:38-46. [PMID: 37979933 DOI: 10.1016/j.niox.2023.11.001] [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: 07/03/2023] [Revised: 09/28/2023] [Accepted: 11/02/2023] [Indexed: 11/20/2023]
Abstract
S-Nitroso-N-acetylpenicillamine (SNAP) is among the most common nitric oxide (NO)-donor molecules and its solid-state photolytic decomposition has potential for inhaled nitric oxide (iNO) therapy. The photochemical NO release kinetics and mechanism were investigated by exposing solid-state SNAP to a narrow-band LED as a function of nominal wavelength and intensity of incident light. The photolytic efficiency, decomposition products, and the photolytic pathways of the SNAP were examined. The maximum light penetration depth through the solid layer of SNAP was determined by an optical microscope and found to be within 100-200 μm, depending on the wavelength of light. The photolysis of solid-state SNAP to generate NO along with the stable thiyl (RS·) radical was confirmed using Electron Spin Resonance (ESR) spectroscopy. The fate of the RS· radical in the solid phase was studied both in the presence and absence of O2 using NMR, IR, ESR, and UPLC-MS. The changes in the morphology of SNAP due to its photolysis were examined using PXRD and SEM. The stable thiyl radical formed from the photolysis of solid SNAP was found to be reactive with another adjacent thiyl radical to form a disulfide (RSSR) or with oxygen to form various sulfonyl and sulfonyl peroxyl radicals {RS(O)xO·, x = 0 to 7}. However, the thiyl radical did not recombine with NO to reform the SNAP. From the PXRD data, it was found that the SNAP loses its crystallinity by generating the NO after photolysis. The initial release of NO during photolysis was increased with increased intensity of light, whereas the maximum light penetration depth was unaffected by light intensity. The knowledge gained about the photochemical reactions of SNAP may provide important insight in designing portable photoinduced NO-releasing devices for iNO therapy.
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Affiliation(s)
- Partha S Sheet
- Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, 48109, USA
| | - Gergely Lautner
- Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, 48109, USA.
| | - Mark E Meyerhoff
- Department of Chemistry, University of Michigan, Ann Arbor, MI, 48109, USA
| | - Steven P Schwendeman
- Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, 48109, USA.
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Hondal RJ. Selenium vitaminology: The connection between selenium, vitamin C, vitamin E, and ergothioneine. Curr Opin Chem Biol 2023; 75:102328. [PMID: 37236134 PMCID: PMC10524500 DOI: 10.1016/j.cbpa.2023.102328] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 04/25/2023] [Accepted: 04/26/2023] [Indexed: 05/28/2023]
Abstract
Selenium is connected to three small molecule antioxidant compounds, ascorbate, α-tocopherol, and ergothioneine. Ascorbate and α-tocopherol are true vitamins, while ergothioneine is a "vitamin-like" compound. Here we review how selenium is connected to all three. Selenium and vitamin E work together as a team to prevent lipid peroxidation. Vitamin E quenches lipid hydroperoxyl radicals and the resulting lipid hydroperoxide is then converted to the lipid alcohol by selenocysteine-containing glutathione peroxidase. Ascorbate reduces the resulting α-tocopheroxyl radical in this reaction back to α-tocopherol with concomitant production of the ascorbyl radical. The ascorbyl radical can be reduced back to ascorbate by selenocysteine-containing thioredoxin reductase. Ergothioneine and ascorbate are both water soluble, small molecule reductants that can reduce free radicals and redox-active metals. Thioredoxin reductase can reduce oxidized forms of ergothioneine. While the biological significance of this is not yet realized, this discovery underscores the centrality of selenium to all three antioxidants.
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Affiliation(s)
- Robert J Hondal
- Department of Biochemistry, 89 Beaumont Ave, Given Laboratory, Room B413, Burlington, VT, 05405, USA.
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Fujii J, Soma Y, Matsuda Y. Biological Action of Singlet Molecular Oxygen from the Standpoint of Cell Signaling, Injury and Death. Molecules 2023; 28:molecules28104085. [PMID: 37241826 DOI: 10.3390/molecules28104085] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 05/11/2023] [Accepted: 05/12/2023] [Indexed: 05/28/2023] Open
Abstract
Energy transfer to ground state triplet molecular oxygen results in the generation of singlet molecular oxygen (1O2), which has potent oxidizing ability. Irradiation of light, notably ultraviolet A, to a photosensitizing molecule results in the generation of 1O2, which is thought to play a role in causing skin damage and aging. It should also be noted that 1O2 is a dominant tumoricidal component that is generated during the photodynamic therapy (PDT). While type II photodynamic action generates not only 1O2 but also other reactive species, endoperoxides release pure 1O2 upon mild exposure to heat and, hence, are considered to be beneficial compounds for research purposes. Concerning target molecules, 1O2 preferentially reacts with unsaturated fatty acids to produce lipid peroxidation. Enzymes that contain a reactive cysteine group at the catalytic center are vulnerable to 1O2 exposure. Guanine base in nucleic acids is also susceptible to oxidative modification, and cells carrying DNA with oxidized guanine units may experience mutations. Since 1O2 is produced in various physiological reactions in addition to photodynamic reactions, overcoming technical challenges related to its detection and methods used for its generation would allow its potential functions in biological systems to be better understood.
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Affiliation(s)
- Junichi Fujii
- Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, Yamagata 990-9585, Japan
| | - Yuya Soma
- Graduate School of Nursing, Yamagata University Faculty of Medicine, Yamagata 990-9585, Japan
| | - Yumi Matsuda
- Graduate School of Nursing, Yamagata University Faculty of Medicine, Yamagata 990-9585, Japan
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Vahalová P, Cifra M. Biological autoluminescence as a perturbance-free method for monitoring oxidation in biosystems. PROGRESS IN BIOPHYSICS AND MOLECULAR BIOLOGY 2023; 177:80-108. [PMID: 36336139 DOI: 10.1016/j.pbiomolbio.2022.10.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 10/20/2022] [Accepted: 10/24/2022] [Indexed: 11/06/2022]
Abstract
Biological oxidation processes are in the core of life energetics, play an important role in cellular biophysics, physiological cell signaling or cellular pathophysiology. Understanding of biooxidation processes is also crucial for biotechnological applications. Therefore, a plethora of methods has been developed for monitoring oxidation so far, each with distinct advantages and disadvantages. We review here the available methods for monitoring oxidation and their basic characteristics and capabilities. Then we focus on a unique method - the only one that does not require input of additional external energy or chemicals - which employs detection of biological autoluminescence (BAL). We highlight the pros and cons of this method and provide an overview of how BAL can be used to report on various aspects of cellular oxidation processes starting from oxygen consumption to the generation of oxidation products such as carbonyls. This review highlights the application potential of this completely non-invasive and label-free biophotonic diagnostic method.
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Affiliation(s)
- Petra Vahalová
- Institute of Photonics and Electronics of the Czech Academy of Sciences, Prague, 18200, Czech Republic
| | - Michal Cifra
- Institute of Photonics and Electronics of the Czech Academy of Sciences, Prague, 18200, Czech Republic.
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Dong Z, Liang P, Guan G, Yin B, Wang Y, Yue R, Zhang X, Song G. Overcoming Hypoxia‐Induced Ferroptosis Resistance via a
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H‐MRI Traceable Core‐Shell Nanostructure. Angew Chem Int Ed Engl 2022; 61:e202206074. [DOI: 10.1002/anie.202206074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Indexed: 11/06/2022]
Affiliation(s)
- Zhe Dong
- State Key Laboratory of Chemo/Biosensing and Chemometrics College of Chemistry and Chemical Engineering Hunan University Changsha 410082 P. R. China
| | - Peng Liang
- State Key Laboratory of Chemo/Biosensing and Chemometrics College of Chemistry and Chemical Engineering Hunan University Changsha 410082 P. R. China
| | - Guoqiang Guan
- State Key Laboratory of Chemo/Biosensing and Chemometrics College of Chemistry and Chemical Engineering Hunan University Changsha 410082 P. R. China
| | - Baoli Yin
- State Key Laboratory of Chemo/Biosensing and Chemometrics College of Chemistry and Chemical Engineering Hunan University Changsha 410082 P. R. China
| | - Youjuan Wang
- State Key Laboratory of Chemo/Biosensing and Chemometrics College of Chemistry and Chemical Engineering Hunan University Changsha 410082 P. R. China
| | - Renye Yue
- State Key Laboratory of Chemo/Biosensing and Chemometrics College of Chemistry and Chemical Engineering Hunan University Changsha 410082 P. R. China
| | - Xiaobing Zhang
- State Key Laboratory of Chemo/Biosensing and Chemometrics College of Chemistry and Chemical Engineering Hunan University Changsha 410082 P. R. China
| | - Guosheng Song
- State Key Laboratory of Chemo/Biosensing and Chemometrics College of Chemistry and Chemical Engineering Hunan University Changsha 410082 P. R. China
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Oxidized Forms of Ergothioneine Are Substrates for Mammalian Thioredoxin Reductase. Antioxidants (Basel) 2022; 11:antiox11020185. [PMID: 35204068 PMCID: PMC8868364 DOI: 10.3390/antiox11020185] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 01/16/2022] [Accepted: 01/17/2022] [Indexed: 11/17/2022] Open
Abstract
Ergothioneine (EGT) is a sulfur-containing amino acid analog that is biosynthesized in fungi and bacteria, accumulated in plants, and ingested by humans where it is concentrated in tissues under oxidative stress. While the physiological function of EGT is not yet fully understood, EGT is a potent antioxidant in vitro. Here we report that oxidized forms of EGT, EGT-disulfide (ESSE) and 5-oxo-EGT, can be reduced by the selenoenzyme mammalian thioredoxin reductase (Sec-TrxR). ESSE and 5-oxo-EGT are formed upon reaction with biologically relevant reactive oxygen species. We found that glutathione reductase (GR) can reduce ESSE, but only with the aid of glutathione (GSH). The reduction of ESSE by TrxR was found to be selenium dependent, with non-selenium-containing TrxR enzymes having little or no ability to reduce ESSE. In comparing the reduction of ESSE by Sec-TrxR in the presence of thioredoxin to that of GR/GSH, we find that the glutathione system is 10-fold more efficient, but Sec-TrxR has the advantage of being able to reduce both ESSE and 5-oxo-EGT directly. This represents the first discovered direct enzymatic recycling system for oxidized forms of EGT. Based on our in vitro results, the thioredoxin system may be important for EGT redox biology and requires further in vivo investigation.
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Geven M, d'Arcy R, Turhan ZY, El-Mohtadi F, Alshamsan A, Tirelli N. Sulfur-based oxidation-responsive polymers. Chemistry, (chemically selective) responsiveness and biomedical applications. Eur Polym J 2021. [DOI: 10.1016/j.eurpolymj.2021.110387] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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Korybalska K, Wisniewska–Elnur J, Trómińska J, Jörres A, Bre¸borowicz A, Witowski J. The Role of the Glyoxalase Pathway in Reducing Mesothelial Toxicity of Glucose Degradation Products. Perit Dial Int 2020. [DOI: 10.1177/089686080602600223] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
BackgroundThe glucose degradation products (GDP) present in conventional peritoneal dialysis fluids (PDF) may exert adverse effects toward human peritoneal mesothelial cells (HPMC). Some GDP can be detoxified by the glyoxalase/glutathione pathway. It has been shown that the addition of glyoxalase I (GLO-I) and reduced glutathione (GSH) to PDF effectively eliminates GDP. We have therefore examined the GLO-I/GSH system in HPMC and assessed the impact of GLO-I/GSH-treated PDF on the viability and function of HPMC.MethodsHeat-sterilized PDF (H-PDF) was incubated in the presence or absence of GLO-I and GSH for 1 hour at 37°C, and then mixed with an equal volume of serum-free M199 medium and applied to HPMC in culture. After 24 hours, HPMC were assessed for viability, the release of interleukin-6, GLO-I activity, and cellular glutathione. The effects were compared to those exerted by filter-sterilized PDF (F-PDF), which was devoid of GDP.ResultsExposure of HPMC to H-PDF resulted in reduced GLO-I activity, GSH depletion, and a decrease in cell viability. Pretreatment of H-PDF with either a combination of GLO-I and GSH or GSH alone markedly reduced inhibitory effects of H-PDF toward HPMC, as measured by cell viability and interleukin-6 generation. Exposure of HPMC to the GSH precursor L-2-oxothiazolidine-carboxylic acid increased cellular GSH and prevented the loss of GLO-I activity in response to H-PDF.ConclusionsExposure to conventional GDP-rich PDF impairs the activity of the glyoxalase/glutathione system in HPMC. Pretreatment of PDF with GSH or replenishment of cellular GSH protects HPMC against GDP-mediated toxicity.
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Affiliation(s)
| | | | - Joanna Trómińska
- Department of Pathophysiology, University Medical School, Poznań, Poland
| | - Achim Jörres
- Department of Nephrology and Medical Intensive Care, Universitätsmedizin Charité, Campus Virchow-Klinikum, Berlin, Germany
| | | | - Janusz Witowski
- Department of Pathophysiology, University Medical School, Poznań, Poland
- Department of Nephrology and Medical Intensive Care, Universitätsmedizin Charité, Campus Virchow-Klinikum, Berlin, Germany
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Khorobrykh S, Havurinne V, Mattila H, Tyystjärvi E. Oxygen and ROS in Photosynthesis. PLANTS (BASEL, SWITZERLAND) 2020; 9:E91. [PMID: 31936893 PMCID: PMC7020446 DOI: 10.3390/plants9010091] [Citation(s) in RCA: 141] [Impact Index Per Article: 28.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Revised: 12/29/2019] [Accepted: 01/02/2020] [Indexed: 12/14/2022]
Abstract
Oxygen is a natural acceptor of electrons in the respiratory pathway of aerobic organisms and in many other biochemical reactions. Aerobic metabolism is always associated with the formation of reactive oxygen species (ROS). ROS may damage biomolecules but are also involved in regulatory functions of photosynthetic organisms. This review presents the main properties of ROS, the formation of ROS in the photosynthetic electron transport chain and in the stroma of chloroplasts, and ROS scavenging systems of thylakoid membrane and stroma. Effects of ROS on the photosynthetic apparatus and their roles in redox signaling are discussed.
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Affiliation(s)
| | | | | | - Esa Tyystjärvi
- Department of Biochemistry/Molecular Plant Biology, University of Turku, FI-20014 Turku, Finland or (S.K.); (V.H.); (H.M.)
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Bittle J, Menezes EC, McCormick ML, Spitz DR, Dailey M, Stevens HE. The Role of Redox Dysregulation in the Effects of Prenatal Stress on Embryonic Interneuron Migration. Cereb Cortex 2019; 29:5116-5130. [PMID: 30877797 PMCID: PMC7199998 DOI: 10.1093/cercor/bhz052] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2018] [Revised: 02/18/2019] [Accepted: 02/22/2019] [Indexed: 01/09/2023] Open
Abstract
Maternal stress during pregnancy is associated with increased risk of psychiatric disorders in offspring, but embryonic brain mechanisms disrupted by prenatal stress are not fully understood. Our lab has shown that prenatal stress delays inhibitory neural progenitor migration. Here, we investigated redox dysregulation as a mechanism for embryonic cortical interneuron migration delay, utilizing direct manipulation of pro- and antioxidants and a mouse model of maternal repetitive restraint stress starting on embryonic day 12. Time-lapse, live-imaging of migrating GAD67GFP+ interneurons showed that normal tangential migration of inhibitory progenitor cells was disrupted by the pro-oxidant, hydrogen peroxide. Interneuron migration was also delayed by in utero intracerebroventricular rotenone. Prenatal stress altered glutathione levels and induced changes in activity of antioxidant enzymes and expression of redox-related genes in the embryonic forebrain. Assessment of dihydroethidium (DHE) fluorescence after prenatal stress in ganglionic eminence (GE), the source of migrating interneurons, showed increased levels of DHE oxidation. Maternal antioxidants (N-acetylcysteine and astaxanthin) normalized DHE oxidation levels in GE and ameliorated the migration delay caused by prenatal stress. Through convergent redox manipula-tions, delayed interneuron migration after prenatal stress was found to critically involve redox dysregulation. Redox biology during prenatal periods may be a target for protecting brain development.
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Affiliation(s)
- Jada Bittle
- Department of Psychiatry, University of Iowa Carver College of Medicine, 1310 PBDB, 169 Newton Rd, Iowa City, IA, USA
- Interdisciplinary Graduate Program in Neuroscience, University of Iowa, 356 Medical Research Center, Iowa City, IA, USA
| | - Edenia C Menezes
- Department of Psychiatry, University of Iowa Carver College of Medicine, 1310 PBDB, 169 Newton Rd, Iowa City, IA, USA
| | - Michael L McCormick
- Free Radical and Radiation Biology Program, Department of Radiation Oncology, University of Iowa Carver College of Medicine, B180 Medical Laboratories, Iowa City, IA, USA
| | - Douglas R Spitz
- Free Radical and Radiation Biology Program, Department of Radiation Oncology, University of Iowa Carver College of Medicine, B180 Medical Laboratories, Iowa City, IA, USA
| | - Michael Dailey
- Interdisciplinary Graduate Program in Neuroscience, University of Iowa, 356 Medical Research Center, Iowa City, IA, USA
- Iowa Neuroscience Institute, University of Iowa, 2312 PBDB, 169 Newton Rd, Iowa City, IA, USA
| | - Hanna E Stevens
- Department of Psychiatry, University of Iowa Carver College of Medicine, 1310 PBDB, 169 Newton Rd, Iowa City, IA, USA
- Interdisciplinary Graduate Program in Neuroscience, University of Iowa, 356 Medical Research Center, Iowa City, IA, USA
- Iowa Neuroscience Institute, University of Iowa, 2312 PBDB, 169 Newton Rd, Iowa City, IA, USA
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Zhang H, Chen J, Yang Y, Wang L, Li Z, Qiu H. Discriminative Detection of Glutathione in Cell Lysates Based on Oxidase-Like Activity of Magnetic Nanoporous Graphene. Anal Chem 2019; 91:5004-5010. [PMID: 30889954 DOI: 10.1021/acs.analchem.8b04779] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
As the most abundant intracellular biothiol, glutathione (GSH) plays a central role in many cellular functions and has been proved to be associated with numerous clinical diseases. Nevertheless, it is still a challenge to detect GSH over other mercaptoamino acids owing to their similar structures and activities. In this paper, magnetic nanoporous graphene (MNPG) nanocomposites were prepared for the first time through partial combustion of graphene oxide (GO) and ferric chloride. Due to the combination of porous graphene and magnetic nanoparticles, the MNPG nanocomposites exhibited large specific surface area, fast mass, and electron transport kinetics, resulting in remarkable oxidase mimic activity and easy separation. On the basis of the inhibition effect of GSH on the MNPG-catalyzed oxidation of thiamine, a novel and simple method for fluorescence determination of GSH was established. The sensor displayed a good linear response in the range of 0.2-20 μM toward GSH with a limit of detection of 0.05 μM. High sensitivity and selectivity facilitated its practical application for discriminative detection of GSH levels in PC12 cell lysates. The presented assay will be a simple and powerful tool to monitor intracellular GSH levels for biomedical diagnosis. Furthermore, the MNPG nanocomposites will provide insights to construct nanoporous graphene-based hybrids and push forward the advancement of porous graphene for wide applications.
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Affiliation(s)
- Haijuan Zhang
- CAS Key Laboratory of Chemistry of Northwestern Plant Resources/Key Laboratory for Natural Medicine of Gansu Province , Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences , Lanzhou 730000 , China
| | - Jia Chen
- CAS Key Laboratory of Chemistry of Northwestern Plant Resources/Key Laboratory for Natural Medicine of Gansu Province , Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences , Lanzhou 730000 , China
| | - Yali Yang
- CAS Key Laboratory of Chemistry of Northwestern Plant Resources/Key Laboratory for Natural Medicine of Gansu Province , Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences , Lanzhou 730000 , China
| | - Li Wang
- CAS Key Laboratory of Chemistry of Northwestern Plant Resources/Key Laboratory for Natural Medicine of Gansu Province , Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences , Lanzhou 730000 , China
| | - Zhan Li
- CAS Key Laboratory of Chemistry of Northwestern Plant Resources/Key Laboratory for Natural Medicine of Gansu Province , Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences , Lanzhou 730000 , China
| | - Hongdeng Qiu
- CAS Key Laboratory of Chemistry of Northwestern Plant Resources/Key Laboratory for Natural Medicine of Gansu Province , Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences , Lanzhou 730000 , China
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Onyango AN. Cellular Stresses and Stress Responses in the Pathogenesis of Insulin Resistance. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2018; 2018:4321714. [PMID: 30116482 PMCID: PMC6079365 DOI: 10.1155/2018/4321714] [Citation(s) in RCA: 79] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/01/2018] [Accepted: 02/18/2018] [Indexed: 12/14/2022]
Abstract
Insulin resistance (IR), a key component of the metabolic syndrome, precedes the development of diabetes, cardiovascular disease, and Alzheimer's disease. Its etiological pathways are not well defined, although many contributory mechanisms have been established. This article summarizes such mechanisms into the hypothesis that factors like nutrient overload, physical inactivity, hypoxia, psychological stress, and environmental pollutants induce a network of cellular stresses, stress responses, and stress response dysregulations that jointly inhibit insulin signaling in insulin target cells including endothelial cells, hepatocytes, myocytes, hypothalamic neurons, and adipocytes. The insulin resistance-inducing cellular stresses include oxidative, nitrosative, carbonyl/electrophilic, genotoxic, and endoplasmic reticulum stresses; the stress responses include the ubiquitin-proteasome pathway, the DNA damage response, the unfolded protein response, apoptosis, inflammasome activation, and pyroptosis, while the dysregulated responses include the heat shock response, autophagy, and nuclear factor erythroid-2-related factor 2 signaling. Insulin target cells also produce metabolites that exacerbate cellular stress generation both locally and systemically, partly through recruitment and activation of myeloid cells which sustain a state of chronic inflammation. Thus, insulin resistance may be prevented or attenuated by multiple approaches targeting the different cellular stresses and stress responses.
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Affiliation(s)
- Arnold N. Onyango
- Department of Food Science and Technology, Jomo Kenyatta University of Agriculture and Technology, P.O. Box 62000, Nairobi 00200, Kenya
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Sierant M, Kulik K, Sochacka E, Szewczyk R, Sobczak M, Nawrot B. Cytochrome c Catalyzes the Hydrogen Peroxide-Assisted Oxidative Desulfuration of 2-Thiouridines in Transfer RNAs. Chembiochem 2018; 19:687-695. [PMID: 29287127 DOI: 10.1002/cbic.201700692] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2017] [Indexed: 12/14/2022]
Abstract
The 5-substituted 2-thiouridines (R5S2Us) present in the first (wobble) position of the anticodon of transfer RNAs (tRNAs) contribute to accuracy in reading mRNA codons and tuning protein synthesis. Previously, we showed that, under oxidative stress conditions in vitro, R5S2Us were sensitive to hydrogen peroxide (H2 O2 ) and that their oxidative desulfuration produced 5-substituted uridines (R5Us) and 4-pyrimidinone nucleosides (R5H2Us) at a ratio that depended on the pH and an R5 substituent. Here, we demonstrate that the desulfuration of 2-thiouridines, either alone or within an RNA/tRNA chain, is catalyzed by cytochrome c (cyt c). Its kinetics are similar to those of Fenton-type catalytic 2-thiouridine (S2U) desulfuration. Cyt c/H2 O2 - and FeII -mediated reactions deliver predominantly 4-pyrimidinone nucleoside (H2U)-type products. The pathway of the cyt c/H2 O2 -peroxidase-mediated S2U→H2U transformation through uridine sulfenic (U-SOH), sulfinic (U-SO2 H), and sulfonic (U-SO3 H) intermediates is confirmed by LC-MS. The cyt c/H2 O2 -mediated oxidative damage of S2U-tRNA may have biological relevance through alteration of the cellular functions of transfer RNA.
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Affiliation(s)
- Małgorzata Sierant
- Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, Lodz, 90-363, Poland
| | - Katarzyna Kulik
- Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, Lodz, 90-363, Poland
| | - Elzbieta Sochacka
- Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, Zeromskiego 116, Lodz, 90-924, Poland
| | - Rafal Szewczyk
- Department of Industrial Microbiology and Biotechnology, Institute of Microbiology, Biotechnology and Immunology, Faculty of Biology and Environmental Protection, University of Lodz, Banacha 12/16, Lodz, 90-237, Poland
| | - Milena Sobczak
- Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, Lodz, 90-363, Poland
| | - Barbara Nawrot
- Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, Lodz, 90-363, Poland
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Bauer G. Autoamplificatory singlet oxygen generation sensitizes tumor cells for intercellular apoptosis-inducing signaling. Mech Ageing Dev 2017; 172:59-77. [PMID: 29137940 DOI: 10.1016/j.mad.2017.11.005] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2017] [Revised: 09/01/2017] [Accepted: 11/01/2017] [Indexed: 11/16/2022]
Abstract
Tumor cells express NADPH oxidase-1 (NOX1) in their membrane and control NOX1-based intercellular reactive oxygen and nitrogen species (ROS/RNS)-dependent apoptosis-inducing signaling through membrane-associated catalase and superoxide dismutase. TREATMENT of tumor cells with high concentrations of H2O2, peroxnitrite, HOCl, or increasing the concentration of cell-derived NO causes initial generation of singlet oxygen and local inactivation of membrane-associated catalase. As a result, free peroxynitrite and H2O2 interact and generate secondary singlet oxygen. Inactivation of further catalase molecules by secondary singlet oxygen leads to auto-amplification of singlet oxygen generation and catalase inactivation. This allows reactivation of intercellular ROS/RNS-signaling and selective apoptosis induction in tumor cells. The initial singlet oxygen generation seems to be the critical point in this complex biochemical multistep mechanism. Initial singlet oxygen generation requires the interaction between distinct tumor cell-derived ROS and RNS and may also depend on either the induction of NO synthase expression or NOX1 activation through the FAS receptor. FAS receptor activation can be achieved by singlet oxygen. Autoamplificatory generation of singlet oxygen through the interaction between peroxynitrite and hydrogen peroxide inherits a rich potential for the establishment of synergistic effects that may be instrumental for novel approaches of tumor therapy with high selectivity towards malignant cells.
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Affiliation(s)
- Georg Bauer
- Institute of Virology, Medical Center - University of Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany.
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16
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Blázquez-Castro A. Direct 1O 2 optical excitation: A tool for redox biology. Redox Biol 2017; 13:39-59. [PMID: 28570948 PMCID: PMC5451181 DOI: 10.1016/j.redox.2017.05.011] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2017] [Revised: 04/30/2017] [Accepted: 05/20/2017] [Indexed: 12/28/2022] Open
Abstract
Molecular oxygen (O2) displays very interesting properties. Its first excited state, commonly known as singlet oxygen (1O2), is one of the so-called Reactive Oxygen Species (ROS). It has been implicated in many redox processes in biological systems. For many decades its role has been that of a deleterious chemical species, although very positive clinical applications in the Photodynamic Therapy of cancer (PDT) have been reported. More recently, many ROS, and also 1O2, are in the spotlight because of their role in physiological signaling, like cell proliferation or tissue regeneration. However, there are methodological shortcomings to properly assess the role of 1O2 in redox biology with classical generation procedures. In this review the direct optical excitation of O2 to produce 1O2 will be introduced, in order to present its main advantages and drawbacks for biological studies. This photonic approach can provide with many interesting possibilities to understand and put to use ROS in redox signaling and in the biomedical field.
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Affiliation(s)
- Alfonso Blázquez-Castro
- Department of Physics of Materials, Faculty of Sciences, Autonomous University of Madrid, Madrid, Spain; Formerly at Aarhus Institute of Advanced Studies (AIAS)/Department of Chemistry, Aarhus University, Aarhus, Denmark.
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17
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The Contribution of Singlet Oxygen to Insulin Resistance. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2017; 2017:8765972. [PMID: 29081894 PMCID: PMC5610878 DOI: 10.1155/2017/8765972] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/24/2017] [Accepted: 08/07/2017] [Indexed: 12/21/2022]
Abstract
Insulin resistance contributes to the development of diabetes and cardiovascular dysfunctions. Recent studies showed that elevated singlet oxygen-mediated lipid peroxidation precedes and predicts diet-induced insulin resistance (IR), and neutrophils were suggested to be responsible for such singlet oxygen production. This review highlights literature suggesting that insulin-responsive cells such as endothelial cells, hepatocytes, adipocytes, and myocytes also produce singlet oxygen, which contributes to insulin resistance, for example, by generating bioactive aldehydes, inducing endoplasmic reticulum (ER) stress, and modifying mitochondrial DNA. In these cells, nutrient overload leads to the activation of Toll-like receptor 4 and other receptors, leading to the production of both peroxynitrite and hydrogen peroxide, which react to produce singlet oxygen. Cytochrome P450 2E1 and cytochrome c also contribute to singlet oxygen formation in the ER and mitochondria, respectively. Endothelial cell-derived singlet oxygen is suggested to mediate the formation of oxidized low-density lipoprotein which perpetuates IR, partly through neutrophil recruitment to adipose tissue. New singlet oxygen-involving pathways for the formation of IR-inducing bioactive aldehydes such as 4-hydroperoxy-(or hydroxy or oxo)-2-nonenal, malondialdehyde, and cholesterol secosterol A are proposed. Strategies against IR should target the singlet oxygen-producing pathways, singlet oxygen quenching, and singlet oxygen-induced cellular responses.
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Umeno A, Biju V, Yoshida Y. In vivo ROS production and use of oxidative stress-derived biomarkers to detect the onset of diseases such as Alzheimer's disease, Parkinson's disease, and diabetes. Free Radic Res 2017; 51:413-427. [PMID: 28372523 DOI: 10.1080/10715762.2017.1315114] [Citation(s) in RCA: 171] [Impact Index Per Article: 21.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Breakthroughs in biochemistry have furthered our understanding of the onset and progression of various diseases, and have advanced the development of new therapeutics. Oxidative stress and reactive oxygen species (ROS) are ubiquitous in biological systems. ROS can be formed non-enzymatically by chemical, photochemical and electron transfer reactions, or as the byproducts of endogenous enzymatic reactions, phagocytosis, and inflammation. Imbalances in ROS homeostasis, caused by impairments in antioxidant enzymes or non-enzymatic antioxidant networks, increase oxidative stress, leading to the deleterious oxidation and chemical modification of biomacromolecules such as lipids, DNA, and proteins. While many ROS are intracellular signaling messengers and most products of oxidative metabolisms are beneficial for normal cellular function, the elevation of ROS levels by light, hyperglycemia, peroxisomes, and certain enzymes causes oxidative stress-sensitive signaling, toxicity, oncogenesis, neurodegenerative diseases, and diabetes. Although the underlying mechanisms of these diseases are manifold, oxidative stress caused by ROS is a major contributing factor in their onset. This review summarizes the relationship between ROS and oxidative stress, with special reference to recent advancements in the detection of biomarkers related to oxidative stress. Further, we will introduce biomarkers for the early detection of neurodegenerative diseases and diabetes, with a focus on our recent work.
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Affiliation(s)
- Aya Umeno
- a Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) , Takamatsu , Kagawa , Japan
| | - Vasudevanpillai Biju
- a Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) , Takamatsu , Kagawa , Japan.,b Laboratory of Molecular Photonics, Research Institute for Electronic Science, Hokkaido University, N20W10 , Kita Ward, Sapporo , Japan
| | - Yasukazu Yoshida
- a Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) , Takamatsu , Kagawa , Japan
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19
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A role for Sel-Plex™, a source of organic selenium in selenised yeast cell wall protein, as a factor that influences meat stability. JOURNAL OF APPLIED ANIMAL NUTRITION 2016. [DOI: 10.1017/jan.2016.6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
SummarySelenium is an important mineral required in the antioxidant system in animals, which is involved with oxidative stability in tissues, particularly membranes, and is involved in various aspects of meat quality and stability on the shelf, due to its protective properties on lipids, preventing rancidity. Se can be supplied in an inorganic or chemically organic form, and it is well known that the latter has beneficial properties and improved functionality in physiological systems compared to the former. Research has shown that organic Se is associated with increased tenderness and the prevention of certain problems in pale exudative meat, discolouration and off-flavours and odours in meat, although this depends on other components of the antioxidant system, such as vitamin E, being present as well. The change in prominence of glutathione peroxidase forms in their interaction with vitamin E in cell membranes is also noted. The following review (the third in a series) details the research that has been conducted into the role of Se in meat stability and related factors, with specific focus on organic forms of Se, namely the commercial product Sel-Plex™ (Alltech Inc, Nicholasville, KY, USA), which is derived from yeast and in which selenium replaces sulphur in methionine forming selenomethionine in yeast protein.
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20
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Moore DR, Kotake Y, Huycke MM. Effects of Iron and Phytic Acid on Production of Extracellular Radicals by Enterococcus faecalis. Exp Biol Med (Maywood) 2016; 229:1186-95. [PMID: 15564446 DOI: 10.1177/153537020422901114] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Enterococcus faecalis is a human intestinal commensal that produces extracellular superoxide, hydrogen peroxide, and hydroxyl radical while colonizing the intestinal tract. To determine whether dietary factors implicated in colorectal cancer affect oxidant production by E. faecalis, radicals were measured in rats colonized with this microorganism while on diets supplemented with iron or phytic acid. Hydroxyl radical activity was measured by assaying for aromatic hydroxylation products of D-phenylalanine using reverse-phase high-performance liquid chromatography and electrochemical detection. In vitro, as expected, iron enhanced, and phytic acid decreased, hydroxyl radical formation by E. faecalis. For rats colonized with E. faecalis given supplemental dietary iron (740 mg elemental iron as ferric phosphate per kg diet) or phytic acid (1.2% w/w), no differences were found in concentrations of urinary ortho- or meta- isomers of D-phenylalanine compared to rats on a basal diet. Aqueous radicals in colonic contents were further assessed ex vivo by electron spin resonance using 5,5-dimethyl-1-pyrroline-N-oxide as a spin trap. Mixtures of thiyl (sulfur-centered) and oxygen-centered radicals were detected across all diets. In vitro, similar spectra were observed when E. faecalis was incubated with hydrogen sulfide, air-oxidized cysteine, or an alkylsulfide, as typical sulfur-containing compounds that might occur in colonic contents. In conclusion, intestinal colonization with E. faecalis in a rat model generates both thiyl and oxygen-centered radicals in colonic contents. Radical formation, however, was not significantly altered by short-term dietary supplementation with iron or phytic acid.
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Affiliation(s)
- Danny R Moore
- The Muchmore Laboratories for Infectious Diseases Research, Research Service, Department of Veterans Affairs Medical Center, Oklahoma City, Oklahoma 73104, USA
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21
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Footitt S, Palleschi S, Fazio E, Palomba R, Finch-Savage WE, Silvestroni L. Ultraweak Photon Emission from the Seed Coat in Response to Temperature and Humidity-A Potential Mechanism for Environmental Signal Transduction in the Soil Seed Bank. Photochem Photobiol 2016; 92:678-87. [PMID: 27389858 PMCID: PMC5031227 DOI: 10.1111/php.12616] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2016] [Accepted: 06/13/2016] [Indexed: 11/29/2022]
Abstract
Seeds beneath the soil sense the changing environment to time germination and seedling emergence with the optimum time of year for survival. Environmental signals first impact with the seed at the seed coat. To investigate whether seed coats have a role in environmental sensing we investigated their ultraweak photon emission (UPE) under the variable temperature, relative humidity and oxygen conditions they could experience in the soil seed bank. Using a custom‐built luminometer we measured UPE intensity and spectra (300–700 nm) from Phaseolus vulgaris seeds, seed coats and cotyledons. UPE was greatest from the internal surface of the seed coat. Seed coat UPE increased concomitantly with both increasing temperature and decreasing relative humidity. Emission was oxygen dependent and it was abolished by treatment with dinitrophenylhydrazine, demonstrating the key role of seed coat carbonyls in the phenomenon. We hypothesize that beneath the soil surface the attenuation of light (virtual darkness: low background noise) enables seeds to exploit UPE for transducing key environmental variables in the soil (temperature, humidity and oxygen) to inform them of seasonal and local temperature patterns. Overall, seed coats were found to have potential as effective transducers of key fluctuating environmental variables in the soil.
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Affiliation(s)
- Steven Footitt
- School of Life Sciences, University of Warwick, Warwickshire, UK.
| | - Simonetta Palleschi
- Department of Haematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy
| | - Eugenio Fazio
- Department of Fundamental and Applied Sciences for Engineering, Sapienza University of Rome, Rome, Italy
| | - Raffaele Palomba
- The National Institute for Insurance against Accidents at Work (INAIL), Rome, Italy
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22
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Winterbourn CC. Revisiting the reactions of superoxide with glutathione and other thiols. Arch Biochem Biophys 2016; 595:68-71. [DOI: 10.1016/j.abb.2015.11.028] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2015] [Revised: 06/01/2015] [Accepted: 09/16/2015] [Indexed: 01/17/2023]
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Endogenous Generation of Singlet Oxygen and Ozone in Human and Animal Tissues: Mechanisms, Biological Significance, and Influence of Dietary Components. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2016; 2016:2398573. [PMID: 27042259 PMCID: PMC4799824 DOI: 10.1155/2016/2398573] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/27/2015] [Accepted: 02/08/2016] [Indexed: 12/18/2022]
Abstract
Recent studies have shown that exposing antibodies or amino acids to singlet oxygen results in the formation of ozone (or an ozone-like oxidant) and hydrogen peroxide and that human neutrophils produce both singlet oxygen and ozone during bacterial killing. There is also mounting evidence that endogenous singlet oxygen production may be a common occurrence in cells through various mechanisms. Thus, the ozone-producing combination of singlet oxygen and amino acids might be a common cellular occurrence. This paper reviews the potential pathways of formation of singlet oxygen and ozone in vivo and also proposes some new pathways for singlet oxygen formation. Physiological consequences of the endogenous formation of these oxidants in human tissues are discussed, as well as examples of how dietary factors may promote or inhibit their generation and activity.
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24
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Czapla-Masztafiak J, Okoń K, Gałka M, Huthwelker T, Kwiatek WM. Investigating the Distribution of Chemical Forms of Sulfur in Prostate Cancer Tissue Using X-ray Absorption Spectroscopy. APPLIED SPECTROSCOPY 2016; 70:264-271. [PMID: 26903562 DOI: 10.1177/0003702815620128] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/09/2015] [Accepted: 06/22/2015] [Indexed: 06/05/2023]
Abstract
The use of synchrotron radiation may shed more light on the study of prostate cancer, one of the leading diseases among men. In the presented study the microbeam setup at the PSI Swiss Light Source combined with fluorescence detected X-ray absorption spectroscopy (XAS) was applied to determine two-dimensional (2D) imaging of distributions of various chemical sulfur forms in prostate cancer tissue sections, since sulfur is considered important and essential in cancer progression. The research focused on prostate tissues obtained during routine prostatectomies on patients suffering from prostate cancer.Our previous studies using μ-XAS point measurements on prostate cancer cell lines showed the differences in fractions of various forms of sulfur between cancerous and non-cancerous cells. Therefore, in this experiment the chosen areas of prostate cancer tissues were scanned to get the full picture of the chemical composition of tissue, which is highly heterogeneous. The incident X-ray beams of energies tuned to spectroscopic features of the near-edge region of sulfur K-edge absorption spectra were used to provide contrast between chemical species presented in the tissue. Next, the relative content of the three main sulfur forms, found in biological systems, was calculated and the results are presented in a form of 2D color maps. These maps are correlated with the microscopic histological image of the scanned area.The main findings show that sulfur occurs in prostate tissue mainly in reduced form. The oxidized form of sulfur is present mostly in prostatic stroma, while sulfur in intermediate oxidation state is present in trace amount.
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Affiliation(s)
| | - Krzysztof Okoń
- Chair of Pathomorphology, Jagiellonian University Medical College, Kraków, Poland
| | - Marek Gałka
- Gabriel Narutowicz City Specialist Hospital, Kraków, Poland
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Trujillo M, Alvarez B, Radi R. One- and two-electron oxidation of thiols: mechanisms, kinetics and biological fates. Free Radic Res 2015; 50:150-71. [PMID: 26329537 DOI: 10.3109/10715762.2015.1089988] [Citation(s) in RCA: 97] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The oxidation of biothiols participates not only in the defense against oxidative damage but also in enzymatic catalytic mechanisms and signal transduction processes. Thiols are versatile reductants that react with oxidizing species by one- and two-electron mechanisms, leading to thiyl radicals and sulfenic acids, respectively. These intermediates, depending on the conditions, participate in further reactions that converge on different stable products. Through this review, we will describe the biologically relevant species that are able to perform these oxidations and we will analyze the mechanisms and kinetics of the one- and two-electron reactions. The processes undergone by typical low-molecular-weight thiols as well as the particularities of specific thiol proteins will be described, including the molecular determinants proposed to account for the extraordinary reactivities of peroxidatic thiols. Finally, the main fates of the thiyl radical and sulfenic acid intermediates will be summarized.
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Affiliation(s)
- Madia Trujillo
- a Departamento de Bioquímica , Facultad de Medicina, Universidad de la República , Montevideo , Uruguay .,b Center for Free Radical and Biomedical Research , Universidad de la República , Montevideo , Uruguay , and
| | - Beatriz Alvarez
- b Center for Free Radical and Biomedical Research , Universidad de la República , Montevideo , Uruguay , and.,c Laboratorio de Enzimología, Facultad de Ciencias , Universidad de la República , Montevideo , Uruguay
| | - Rafael Radi
- a Departamento de Bioquímica , Facultad de Medicina, Universidad de la República , Montevideo , Uruguay .,b Center for Free Radical and Biomedical Research , Universidad de la República , Montevideo , Uruguay , and
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26
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Mattila H, Khorobrykh S, Havurinne V, Tyystjärvi E. Reactive oxygen species: Reactions and detection from photosynthetic tissues. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY 2015; 152:176-214. [PMID: 26498710 DOI: 10.1016/j.jphotobiol.2015.10.001] [Citation(s) in RCA: 64] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/11/2015] [Revised: 09/30/2015] [Accepted: 10/01/2015] [Indexed: 12/22/2022]
Abstract
Reactive oxygen species (ROS) have long been recognized as compounds with dual roles. They cause cellular damage by reacting with biomolecules but they also function as agents of cellular signaling. Several different oxygen-containing compounds are classified as ROS because they react, at least with certain partners, more rapidly than ground-state molecular oxygen or because they are known to have biological effects. The present review describes the typical reactions of the most important ROS. The reactions are the basis for both the detection methods and for prediction of reactions between ROS and biomolecules. Chemical and physical methods used for detection, visualization and quantification of ROS from plants, algae and cyanobacteria will be reviewed. The main focus will be on photosynthetic tissues, and limitations of the methods will be discussed.
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Affiliation(s)
- Heta Mattila
- Department of Biochemistry/Molecular Plant Biology, University of Turku, 20014 Turku, Finland
| | - Sergey Khorobrykh
- Department of Biochemistry/Molecular Plant Biology, University of Turku, 20014 Turku, Finland
| | - Vesa Havurinne
- Department of Biochemistry/Molecular Plant Biology, University of Turku, 20014 Turku, Finland
| | - Esa Tyystjärvi
- Department of Biochemistry/Molecular Plant Biology, University of Turku, 20014 Turku, Finland.
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27
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Smirnova GV, Muzyka NG, Ushakov VY, Tyulenev AV, Oktyabrsky ON. Extracellular superoxide provokes glutathione efflux from Escherichia coli cells. Res Microbiol 2015; 166:609-17. [DOI: 10.1016/j.resmic.2015.07.007] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2015] [Revised: 06/23/2015] [Accepted: 07/06/2015] [Indexed: 11/28/2022]
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Glutathione modifies the oxidation products of 2'-deoxyguanosine by singlet molecular oxygen. Arch Biochem Biophys 2015; 586:33-44. [PMID: 26427352 DOI: 10.1016/j.abb.2015.09.020] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2015] [Revised: 09/20/2015] [Accepted: 09/25/2015] [Indexed: 11/21/2022]
Abstract
The oxidation of the free nucleoside 2'-deoxyguanosine (dGuo) by singlet molecular oxygen ((1)O2) has been studied over the three last decades due to the major role of DNA oxidation products in process such as ageing, mutation and carcinogenesis. In the present work we investigated the dGuo oxidation by (1)O2 in the presence of the important low molecular antioxidant, glutathione, in its reduced (GSH) and oxidized (GSSG) forms. There were applied different conditions of concentration, pH, time of incubation, and the use of a [(18)O]-labeled thermolabile endoperoxide naphthalene derivative as a source of [(18)O]-labeled (1)O2. Data was obtained through high performance liquid chromatography (HPLC) and HPLC coupled to micrOTOF Q-II analysis of the main oxidation products: the diastereomers of spiroiminodihydantoin-2'-deoxyribonucleosides (dSp) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo). An intriguing result was that 8-oxodGuo levels increased by 100 fold when dGuo was oxidized by (1)O2 in the presence of GSH and by 2 fold in the presence of GSSG, while dSp levels dropped to zero for both conditions. All data from dGuo, 8-oxodGuo and dSp quantification together with the analysis of residual GSH/GSSG content in each sample strongly suggest that glutathione modifies the mechanism of dGuo oxidation by (1)O2 by disfavoring the pathway of dSp formation.
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Singh B, Das RS, Banerjee R, Mukhopadhyay S. Uncatalyzed and copper(II) catalyzed oxidation of glutathione by Co(III)2 bound superoxide complex. Inorganica Chim Acta 2014. [DOI: 10.1016/j.ica.2014.03.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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30
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Đurović MD, Bugarčić ŽD, Heinemann FW, van Eldik R. Substitution versus redox reactions of gold(iii) complexes with l-cysteine, l-methionine and glutathione. Dalton Trans 2014; 43:3911-21. [DOI: 10.1039/c3dt53140f] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
The reactions of [AuCl4]−, [Au(terpy)Cl]2+, [Au(bpma)Cl]2+ and [Au(dien)Cl]2+ with l-cysteine, l-methionine and glutathione were examined using stopped-flow, cyclovoltammetry, 1H NMR and ESI-MS techniques.
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Affiliation(s)
| | | | - Frank W. Heinemann
- Inorganic Chemistry
- Department of Chemistry and Pharmacy
- University of Erlangen-Nürnberg
- 91058 Erlangen, Germany
| | - Rudi van Eldik
- Inorganic Chemistry
- Department of Chemistry and Pharmacy
- University of Erlangen-Nürnberg
- 91058 Erlangen, Germany
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31
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Gruhlke MCH, Slusarenko AJ. The biology of reactive sulfur species (RSS). PLANT PHYSIOLOGY AND BIOCHEMISTRY : PPB 2012; 59:98-107. [PMID: 22541352 DOI: 10.1016/j.plaphy.2012.03.016] [Citation(s) in RCA: 164] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/29/2012] [Accepted: 03/31/2012] [Indexed: 05/22/2023]
Abstract
Sulfur is an essential and quantitatively important element for living organisms. Plants contain on average approximately 1 g S kg⁻¹ dry weight (for comparison plants contain approximately 15 g N kg⁻¹ dry weight). Sulfur is a constituent of many organic molecules, for example amino acids such as cysteine and methionine and the small tripeptide glutathione, but sulfur is also essential in the form of Fe-S clusters for the activity of many enzymes, particularly those involved in redox reactions. Sulfur chemistry is therefore important. In particular, sulfur in the form of thiol groups is central to manifold aspects of metabolism. Because thiol groups are oxidized and reduced easily and reversibly, the redox control of cellular metabolism has become an increasing focus of research. In the same way that oxygen and nitrogen have reactive species (ROS and RNS), sulfur too can form reactive molecular species (RSS), for example when a -SH group is oxidized. Indeed, several redox reactions occur via RSS intermediates. Several naturally occurring S-containing molecules are themselves RSS and because they are physiologically active they make up part of the intrinsic plant defence repertoire against herbivore and pathogen attack. Furthermore, RSS can also be used as redox-active pharmacological tools to study cell metabolism. The aim of this review is to familiarize the general reader with some of the chemical concepts, terminology and biology of selected RSS.
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Affiliation(s)
- Martin C H Gruhlke
- Department of Plant Physiology (BioIII), RWTH Aachen University, D-52056 Aachen, Germany
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32
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Al-Abbasi FA. Acrylonitrile-induced gastric toxicity in rats: the role of xanthine oxidase. Med Sci Monit 2012; 18:BR208-14. [PMID: 22648241 PMCID: PMC3560737 DOI: 10.12659/msm.882896] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2011] [Accepted: 12/08/2011] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND Acrylonitrile (ACN) is an extensively produced aliphatic nitrile. The gastrointestinal tract is an important target organ for ACN toxicity. The objective of the present study was to investigate the role of xanthine oxidase (XO) in ACN-induced gastric toxicity in rats. MATERIAL/METHODS We assessed the effect of ACN on oxidative stress parameters as xanthine oxidase (XO) and total xanthine dehydrogenase (XD)/ XO activity, superoxide anion (O(2)(.-)) production, reduced glutathione (GSH) levels and lipid peroxidation in gastric tissues. RESULTS A single oral dose of ACN (25 mg/kg) caused a significant enhancement in XO activity. ACN also caused a significant depletion of GSH levels, enhanced O(2)(.-) production and increased lipid peroxidation in the time-course experiment. In the dose-response experiment, ACN accelerated the conversion of XD to XO, with a significant depletion of gastric GSH in a dose-related manner. A strong negative correlation existed between the levels of GSH and the percentage enhancement in XO activity (r =-0.997). (O(2)(.-)) production and malondialdehyde (MDA) formation were significantly elevated in a dose-related manner. Pretreatment with allopurinol (50 mg/kg) significantly protected against ACN-induced rise in XO activity, depletion of GSH, and elevated production of (O(2)(.-)). However, pretreatment with diethyl maleate (DEM; 100 mg/kg) significantly aggravated the ACN-induced GSH depletion and rise in XO activity. Furthermore, DEM significantly enhanced (O(2)(.-)) and MDA production. CONCLUSIONS The present study indicates that enhancement of XO activity could be implicated in ACN-induced gastric damage in rats.
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Affiliation(s)
- Fahad A Al-Abbasi
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
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Qin Y, Pan X, Tang TT, Zhou L, Gong XG. Anti-proliferative effects of the novel squamosamide derivative (FLZ) on HepG2 human hepatoma cells by regulating the cell cycle-related proteins are associated with decreased Ca(2+)/ROS levels. Chem Biol Interact 2011; 193:246-53. [PMID: 21835169 DOI: 10.1016/j.cbi.2011.07.004] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2011] [Accepted: 07/25/2011] [Indexed: 10/17/2022]
Abstract
FLZ is a synthetic novel squamosamide derivative and has previously been proved to be a potential drug for Parkinson's disease and Alzheimer's disease. FLZ has strong antioxidant activity, which implies that FLZ could eliminate excessive intracellular reactive oxygen species (ROS) in tumor cells and induce a pathway related to low cellular ROS levels, thereby inhibiting tumor cells proliferation. However, few reports have focused on the antitumor effects of FLZ. In this study, we investigated the antitumor efficacy of FLZ in HepG2 cells and the mechanism of cell growth inhibition. FLZ effectively inhibited HepG2 cell proliferation in a dose- and time-dependent manner; meanwhile, it was minimally toxic to normal cells. FLZ induced a significant decrease in oxidative stress through elimination of excessive intracellular ROS and strengthening of the glutathione antioxidant system. In addition, FLZ can effectively attenuate redundant [Ca(2+)](i), thereby avoiding uncontrolled amplification by Ca(2+)/ROS positive feedback. Furthermore, Western blot showed that FLZ inhibited phosphorylation of Akt and retinoblastoma protein (Rb), down-regulated the expressions of cyclin D1, cyclin E, cyclin-dependent kinase 2 (CDK2), and enhanced the expression of CDK inhibitor p27(kip1), while did not affect CDK4 expression. These results suggest that FLZ has potent anti-proliferative activity against malignant human hepatoma cells via modulation of the expression or activation of cell-cycle regulatory proteins, which are associated with decreased Ca(2+)/ROS levels, and indicate that FLZ is a potential liver cancer drug worthy of further research and development.
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Affiliation(s)
- Yong Qin
- Institute of Biochemistry, College of Life Sciences, Zhejiang University, PR China
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34
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Roos G, Messens J. Protein sulfenic acid formation: from cellular damage to redox regulation. Free Radic Biol Med 2011; 51:314-26. [PMID: 21605662 DOI: 10.1016/j.freeradbiomed.2011.04.031] [Citation(s) in RCA: 196] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2010] [Revised: 03/31/2011] [Accepted: 04/17/2011] [Indexed: 01/17/2023]
Abstract
Protein sulfenic acid formation has long been regarded as unwanted damage caused by reactive oxygen species (ROS). However, over the past 10 years, accumulating evidence has shown that the reversible oxidation of cysteine thiol groups to sulfenic acid functions as a redox-based signal transduction mechanism. Here, we review the mechanisms of sulfenic acid formation by ROS. We present some of the most important roles played by sulfenic acids in living cells as well as the pathways that regulate sulfenic acid formation. We highlight the experimental tools that have been developed to study the cellular sulfenome and show how computational approaches might help to better understand the mechanisms of sulfenic acid formation.
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Affiliation(s)
- Goedele Roos
- Department of Molecular and Cellular Interactions, Flanders Institute for Biotechnology, VIB, B-1050 Brussels, Belgium
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35
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Furukawa A, Oikawa S, Harada K, Sugiyama H, Hiraku Y, Murata M, Shimada A, Kawanishi S. Oxidatively generated DNA damage induced by 3-amino-5-mercapto-1,2,4-triazole, a metabolite of carcinogenic amitrole. Mutat Res 2010; 694:7-12. [PMID: 20732334 DOI: 10.1016/j.mrfmmm.2010.08.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2010] [Revised: 08/09/2010] [Accepted: 08/13/2010] [Indexed: 05/29/2023]
Abstract
Amitrole (3-amino-1,2,4-triazole) is a widely used herbicide. Amitrole induces thyroid and liver tumors in rodents. However, the mechanism of carcinogenesis by amitrole remains to be clarified. To clarify the mechanism of carcinogenesis induced by amitrole, we investigated the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a characteristic of oxidatively generated DNA damage, by an amitrole metabolite, 3-amino-5-mercapto-1,2,4-triazole (AMT), in the presence of Cu(II). The amount of 8-oxodG was increased by AMT in the presence of Cu(II). AMT-induced 8-oxodG formation was enhanced in deuterium oxide (D₂O), which prolongs the half life of singlet oxygen (¹O₂), more than that in H₂O. Sodium azide and 1,4-diazabicyclo[2,2,2]-octane (DABCO), potent and relatively specific scavengers of ¹O₂, inhibited AMT-mediated 8-oxodG formation. Bathocuproine, a Cu(I) chelator, also inhibited the 8-oxodG formation. On the other hand, typical OH scavengers did not inhibit the generation of 8-oxodG. AMT plus Cu(II) also induced piperidine-labile DNA lesions frequently at every guanine residue. These results suggest that ¹O₂ and Cu(I) play an important role in DNA damage induced by AMT. It is concluded that oxidatively generated DNA damage induced by AMT via the generation of ¹O₂ may contribute to carcinogenicity of amitrole.
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Affiliation(s)
- Ayako Furukawa
- Department of Pathology, Institute for Developmental Research, Aichi Human Service Center, Aichi 480-0392, Japan
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36
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Leopold JA, Loscalzo J. Oxidative risk for atherothrombotic cardiovascular disease. Free Radic Biol Med 2009; 47:1673-706. [PMID: 19751821 PMCID: PMC2797369 DOI: 10.1016/j.freeradbiomed.2009.09.009] [Citation(s) in RCA: 128] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2009] [Revised: 08/31/2009] [Accepted: 09/06/2009] [Indexed: 02/07/2023]
Abstract
In the vasculature, reactive oxidant species, including reactive oxygen, nitrogen, or halogenating species, and thiyl, tyrosyl, or protein radicals may oxidatively modify lipids and proteins with deleterious consequences for vascular function. These biologically active free radical and nonradical species may be produced by increased activation of oxidant-generating sources and/or decreased cellular antioxidant capacity. Once formed, these species may engage in reactions to yield more potent oxidants that promote transition of the homeostatic vascular phenotype to a pathobiological state that is permissive for atherothrombogenesis. This dysfunctional vasculature is characterized by lipid peroxidation and aberrant lipid deposition, inflammation, immune cell activation, platelet activation, thrombus formation, and disturbed hemodynamic flow. Each of these pathobiological states is associated with an increase in the vascular burden of free radical species-derived oxidation products and, thereby, implicates increased oxidant stress in the pathogenesis of atherothrombotic vascular disease.
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Affiliation(s)
- Jane A Leopold
- Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
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37
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38
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Chiou JF, Wang YH, Jou MJ, Liu TZ, Shiau CY. Verteporfin-photoinduced apoptosis in HepG2 cells mediated by reactive oxygen and nitrogen species intermediates. Free Radic Res 2009; 44:155-70. [DOI: 10.3109/10715760903380458] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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39
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Kataoka T, Yoshimoto M, Nakagawa S, Mizuguchi Y, Taguchi T, Yamaoka K. Basic study on active changes in biological function of mouse liver graft in cold storage after low-dose x-irradiation. J Clin Biochem Nutr 2009; 45:219-26. [PMID: 19794932 PMCID: PMC2735636 DOI: 10.3164/jcbn.09-06] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2009] [Accepted: 04/27/2009] [Indexed: 11/30/2022] Open
Abstract
We previously reported that low-dose X-irradiation alleviates ischemia-reperfusion injury such as mouse paw edema. In this study, we examined active changes in the biological function of mouse liver grafts in cold storage after low-dose X-irradiation. Mouse livers were sham-irradiated or were irradiated with 0.25, 0.5, 1.0, or 5.0 Gy of X-ray and stored for 4, 8, 24, or 48 h in preservation or saline solution. The results show that storage for 24 h in saline solution after 0.5 Gy irradiation significantly increased the activity of superoxide dismutase (SOD) and catalase. Following storage for 4, 8, or 48 h in preservation solution, lipid peroxide levels of the 0.5 Gy irradiated group were significantly lower than those of the sham irradiated group. Following storage for 24 h in preservation solution, the activity of SOD and catalase of the 1.0 Gy irradiated group were significantly higher than those of the sham irradiated group. Hepatocytes stored in saline solution were vacuolated. However, no vacuole formation was observed in hepatocytes stored in preservation solution. These findings suggest that low-dose irradiation significantly activates antioxidative functions of liver grafts. Moreover, the dose at which enhancement of antioxidative function occurs in livers stored in preservation solution, which contains glutathione, is significantly higher than that in saline solution.
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Affiliation(s)
| | | | | | | | | | - Kiyonori Yamaoka
- Graduate School of Health Sciences, Okayama University, 5-1 Shikata-cho, 2-chome, Okayama 700-8558, Japan
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40
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Superoxide radicals increase transforming growth factor-β1 and collagen release from human lung fibroblasts via cellular influx through chloride channels. Toxicol Appl Pharmacol 2009; 237:111-8. [DOI: 10.1016/j.taap.2009.02.019] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2008] [Revised: 02/12/2009] [Accepted: 02/17/2009] [Indexed: 11/20/2022]
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41
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Dick RA, Kanne DB, Casida JE. Nitroso-Imidacloprid Irreversibly Inhibits Rabbit Aldehyde Oxidase. Chem Res Toxicol 2007; 20:1942-6. [DOI: 10.1021/tx700265r] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
- Ryan A. Dick
- Environmental Chemistry and Toxicology Laboratory, Department of Environmental Science, Policy and Management, University of California, Berkeley, California 94720-3112
| | - David B. Kanne
- Environmental Chemistry and Toxicology Laboratory, Department of Environmental Science, Policy and Management, University of California, Berkeley, California 94720-3112
| | - John E. Casida
- Environmental Chemistry and Toxicology Laboratory, Department of Environmental Science, Policy and Management, University of California, Berkeley, California 94720-3112
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42
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Lu M, Bi CS, Gong XG, Chen HM, Sheng XH, Deng TL, Xu KD. Anti-proliferative effects of recombinant iron superoxide dismutase on HepG2 cells via a redox-dependent PI3k/Akt pathway. Appl Microbiol Biotechnol 2007; 76:193-201. [PMID: 17387468 DOI: 10.1007/s00253-007-0939-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2006] [Revised: 03/08/2007] [Accepted: 03/08/2007] [Indexed: 11/29/2022]
Abstract
The coding sequence for an iron superoxide dismutase (fe-sod) was amplified from the Nostoc commune genome. Recombinant Fe-SOD was overexpressed in Escherichia coli, accounting for approximately 76% of total bacterial protein. Fe-SOD was purified from bacterial lysate by Ni-NTA column chromatography and used to generate an anti-SOD antibody. The purified Fe-SOD was encapsulated in liposomes and delivered to HepG2 liver tumor cells to eliminate cellular superoxide anions. The SOD-loaded cells exhibited lower reactive oxygen species (ROS) levels and higher reduced glutathione (GSH) levels. In Fe-SOD-treated cells, the cell cycle was delayed in the G(1) phase, and HepG2 cell growth slowed in association with dephosphorylation of the serine-threonine kinase Akt. Low-dose H(2)O(2) stimulated Akt phosphorylation, implying that Akt activation in HepG2 cells is redox-sensitive. Akt phosphorylation was abrogated by phosphatidylinositol 3-kinase (PI3K) inhibitors, suggesting that PI3K is an upstream mediator of Akt activation in HepG2 cells. This study provides insight into recombinant Fe-SOD-induced signaling mechanisms in liver tumor cells and suggests the feasibility of using Fe-SOD as an antitumor agent.
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Affiliation(s)
- Min Lu
- Institute of Biochemistry, Zhejiang University, Hangzhou, People's Republic of China
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Campbell AK, Hallett MB, Weeks I. Chemiluminescence as an analytical tool in cell biology and medicine. METHODS OF BIOCHEMICAL ANALYSIS 2006; 31:317-416. [PMID: 3894883 DOI: 10.1002/9780470110522.ch7] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
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44
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Russo A, Bump EA. Detection and quantitation of biological sulfhydryls. METHODS OF BIOCHEMICAL ANALYSIS 2006; 33:165-241. [PMID: 3282150 DOI: 10.1002/9780470110546.ch5] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
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45
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Lu M, Gong X, Lu Y, Guo J, Wang C, Pan Y. Molecular Cloning and Functional Characterization of a Cell-permeable Superoxide Dismutase Targeted to Lung Adenocarcinoma Cells. J Biol Chem 2006; 281:13620-13627. [PMID: 16551617 DOI: 10.1074/jbc.m600523200] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
In clinical oncology, many trials with superoxide dismutase (SOD) have failed to demonstrate antitumor ability and in many cases even caused deleterious effects because of low tumor-targeting ability. In the current research, the Nostoc commune Fe-SOD coding sequence was amplified from genomic DNA. In addition, the single chain variable fragment (ScFv) was constructed from the cDNA of an LC-1 hybridoma cell line secreting anti-lung adenocarcinoma monoclonal antibody. After modification, the SOD and ScFv were fused and co-expressed, and the resulting fusion protein produced SOD and LC-1 antibody activity. Tracing SOD-ScFv by fluorescein isothiocyanate and superoxide anions (O2*-) in SPC-A-1 cells showed that the fusion protein could recognize and enter SPC-A-1 cells to eliminate O2*-. The lower oxidative stress resulting from the decrease in cellular O2*- delayed the cell cycle at G1 and significantly slowed SPC-A-1 cell growth in association with the dephosphorylation of the serine-threonine protein kinase Akt and expression of p27kip1. The tumor-targeting fusion protein resulting from this research overcomes two disadvantages of SODs previously used in the clinical setting, the inability to target tumor cells or permeate the cell membrane. These findings lay the groundwork for development of an efficient antitumor drug targeted by the ScFv.
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Affiliation(s)
- Min Lu
- Institute of Biochemistry, Zhejiang University, Hangzhou, 310027, China
| | - Xingguo Gong
- Institute of Biochemistry, Zhejiang University, Hangzhou, 310027, China.
| | - Yuwen Lu
- Institute of Biochemistry, Zhejiang University, Hangzhou, 310027, China
| | - Jianjun Guo
- Institute of Biochemistry, Zhejiang University, Hangzhou, 310027, China
| | - Chenhui Wang
- Institute of Biochemistry, Zhejiang University, Hangzhou, 310027, China
| | - Yuanjiang Pan
- Institute of Chemical Biology and Pharmaceutical Chemistry, Zhejiang University, Hangzhou, 310027, China.
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46
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Lee JS, Ma YB, Choi KS, Park SY, Baek SH, Park YM, Zu K, Zhang H, Ip C, Kim YH, Park EM. Neural Network‐Based Analysis of Thiol Proteomics Data in Identifying Potential Selenium Targets. Prep Biochem Biotechnol 2006; 36:37-64. [PMID: 16428138 DOI: 10.1080/10826060500388512] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
Generation of a monomethylated selenium metabolite is critical for the anticancer activity of selenium. Because of its strong nucleophilicity, the metabolite can react directly with protein thiols to cause redox modification. Here, we report a neural network-based analysis to identify potential selenium targets. A reactive thiol specific reagent, BIAM, was used to monitor thiol proteome changes on 2D gel. We constructed a dynamic model and evaluated the relative importance of proteins mediating the cellular responses to selenium. Information from this study will provide new clues to unravel mechanisms of anticancer action of selenium. High impact selenium targets could also serve as biomarkers to gauge the efficacy of selenium chemoprevention.
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Affiliation(s)
- Jong-Sik Lee
- School of Computer Science & Engineering, Inha University, Korea
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47
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Parvatiyar K, Alsabbagh EM, Ochsner UA, Stegemeyer MA, Smulian AG, Hwang SH, Jackson CR, McDermott TR, Hassett DJ. Global analysis of cellular factors and responses involved in Pseudomonas aeruginosa resistance to arsenite. J Bacteriol 2005; 187:4853-64. [PMID: 15995200 PMCID: PMC1169530 DOI: 10.1128/jb.187.14.4853-4864.2005] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
The impact of arsenite [As(III)] on several levels of cellular metabolism and gene regulation was examined in Pseudomonas aeruginosa. P. aeruginosa isogenic mutants devoid of antioxidant enzymes or defective in various metabolic pathways, DNA repair systems, metal storage proteins, global regulators, or quorum sensing circuitry were examined for their sensitivity to As(III). Mutants lacking the As(III) translocator (ArsB), superoxide dismutase (SOD), catabolite repression control protein (Crc), or glutathione reductase (Gor) were more sensitive to As(III) than wild-type bacteria. The MICs of As(III) under aerobic conditions were 0.2, 0.3, 0.8, and 1.9 mM for arsB, sodA sodB, crc, and gor mutants, respectively, and were 1.5- to 13-fold less than the MIC for the wild-type strain. A two-dimensional gel/matrix-assisted laser desorption ionization-time of flight analysis of As(III)-treated wild-type bacteria showed significantly (>40-fold) increased levels of a heat shock protein (IbpA) and a putative allo-threonine aldolase (GlyI). Smaller increases (up to 3.1-fold) in expression were observed for acetyl-coenzyme A acetyltransferase (AtoB), a probable aldehyde dehydrogenase (KauB), ribosomal protein L25 (RplY), and the probable DNA-binding stress protein (PA0962). In contrast, decreased levels of a heme oxygenase (HemO/PigA) were found upon As(III) treatment. Isogenic mutants were successfully constructed for six of the eight genes encoding the aforementioned proteins. When treated with sublethal concentrations of As(III), each mutant revealed a marginal to significant lag period prior to resumption of apparent normal growth compared to that observed in the wild-type strain. Our results suggest that As(III) exposure results in an oxidative stress-like response in P. aeruginosa, although activities of classic oxidative stress enzymes are not increased. Instead, relief from As(III)-based oxidative stress is accomplished from the collective activities of ArsB, glutathione reductase, and the global regulator Crc. SOD appears to be involved, but its function may be in the protection of superoxide-sensitive sulfhydryl groups.
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Affiliation(s)
- Kislay Parvatiyar
- Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, OH 45267-0524, USA
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48
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Kalayci A, Ozturk A, Ozturk K, Karagozoglu E, Dolanmaz D. Superoxide dismutase and glutathione peroxidase enzyme activities in larynx carcinoma. Acta Otolaryngol 2005; 125:312-5. [PMID: 15966704 DOI: 10.1080/00016480410023074] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
CONCLUSIONS It can be concluded that these changes are related to damage at the DNA level or to the inhibitory effects of tumor promoters. Increases in GSH-Px activities may be related to the independence of this enzyme from the suppressive effects of tumor promoters. This study and others in the literature show that it is not possible to generalize the activities of SOD and GSH-Px in cancer. OBJECTIVE There has been growing interest in the role of free radicals as a cause of cancer. It has been suggested that an increase in activated forms of oxygen in cells due to overproduction and/or the inability to destroy them may lead to severe damage of cell structures. As a result of these changes, some chromosomal aberrations and carcinogenesis may develop. Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) are two important antioxidant enzymes involved in enzymatic antioxidant defense mechanisms. To our knowledge there have been no previous studies in the literature investigating the activities of SOD and GSH-Px in laryngeal cancer. MATERIAL AND METHODS The study subjects comprised 10 male patients (age range 43-76 years) with laryngeal carcinoma and 10 healthy controls (4 males, 6 females; age range 40-69 years) with intraoral hyperplastic fibrous tissue. Homogenate SOD and GSH-Px activities were measured using commercially available kits. RESULTS GSH-Px levels were significantly increased in the cancerous tissues compared with cancer-free adjacent tissues and fibrous hyperplasia tissues (p < 0.05), whereas there was no significant difference between SOD activities (p > 0.05). There was also no significant difference between GSH-Px activity in cancer-free adjacent tissues and fibrous hyperplasia tissues (p > 0.05).
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Affiliation(s)
- Abdullah Kalayci
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Selcuk University, Konya, Turkey.
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49
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Elsayed NM, Omaye ST. Biochemical changes in mouse lung after subcutaneous injection of the sulfur mustard 2-chloroethyl 4-chlorobutyl sulfide. Toxicology 2004; 199:195-206. [PMID: 15147793 DOI: 10.1016/j.tox.2004.02.020] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2003] [Revised: 02/09/2004] [Accepted: 02/19/2004] [Indexed: 11/15/2022]
Abstract
Sulfur mustard (HD) is a vesicant-type chemical warfare agent (CWA) introduced in World War I which continues to be produced, stockpiled, and occasionally deployed by some countries, and could be used potentially by terrorists. Exposure to HD can cause erythema, blisters, corneal opacity, and airway damage. We have reported previously that subcutaneous (SC) injection of immunodeficient athymic nude mice with the half mustard butyl 2-chloroethyl sulfide (BCS) causes systemic biochemical changes in several organs distal to the exposure site. In the present study, we examined the response of non-immunodeficient Swiss Webster mice to the mustard, 2-chloroethyl 4-chlorobutyl sulfide (CECBS). In a pilot study, we found that a single SC injection of 20-25 microl/mouse causes death within 24h. Consequently, we used 5 microl/mouse (approx. 0.017 mg/kg body weight) of neat CECBS or an equal volume of saline as control. We examined the lungs after 1, 24, and 48 h for biochemical changes including total and oxidized glutathione, protein, DNA, and lipid peroxidation contents in tissue homogenate, and superoxide dismutase, catalase, glucose-6-phosphate dehydrogenase, and glutathione S-transferases activities in the cytosol. After 1h and/or 24h, we found statistically significant changes that were resolved by 48 h. These changes mimicked those of HD and BCS and were generally consistent with free radical-mediated oxidative stress. The implications of these observations are two-fold. First, dermal exposure to low-dose mustard gas could elicit systemic changes impacting distal organs such as the lungs. It also suggests that antioxidants could potentially modulate the response and reduce the damage. Second, although the use of known CWAs such as HD is prohibited, analogs that are not recognized as agents are as toxic and could be dangerous if acquired and used by potential terrorists.
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Affiliation(s)
- Nabil M Elsayed
- Department of Nutrition and Environmental Sciences and Health, Graduate Program, University of Nevada at Reno, Reno, NV, USA.
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50
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Schauer RJ, Kalmuk S, Gerbes AL, Leiderer R, Meissner H, Schildberg FW, Messmer K, Bilzer M. Intravenous administration of glutathione protects parenchymal and non-parenchymal liver cells against reperfusion injury following rat liver transplantation. World J Gastroenterol 2004; 10:864-70. [PMID: 15040034 PMCID: PMC4726997 DOI: 10.3748/wjg.v10.i6.864] [Citation(s) in RCA: 52] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: To investigated the effects of intravenous administration of the antioxidant glutathione (GSH) on reperfusion injury following liver transplantation.
METHODS: Livers of male Lewis rats were transplanted after 24 h of hypothermic preservation in University of Wisconsin solution in a syngeneic setting. During a 2-h reperfusion period either saline (controls, n = 8) or GSH (50 or 100 μmol/(h·kg), n = 5 each) was continuously administered via the jugular vein.
RESULTS: Two hours after starting reperfusion plasma ALT increased to 1 457 ± 281 U/L (mean ± SE) in controls but to only 908 ± 187 U/L (P < 0.05) in animals treated with 100 μmol GSH/(h·kg). No protection was conveyed by 50 μmol GSH/(h·kg). Cytoprotection was confirmed by morphological findings on electron microscopy: GSH treatment prevented detachment of sinusoidal endothelial cells (SEC) as well as loss of microvilli and mitochondrial swelling of hepatocytes. Accordingly, postischemic bile flow increased 2-fold. Intravital fluorescence microscopy revealed a nearly complete restoration of sinusoidal blood flow and a significant reduction of leukocyte adherence to sinusoids and postsinusoidal venules. Following infusion of 50 μmol and 100 μmol GSH/(h·kg), plasma GSH increased to 65 ± 7 mol/L and 97 ± 18 mol/L, but to only 20 ± 3 mol/L in untreated recipients. Furthermore, plasma glutathione disulfide (GSSG) increased to 7.5 ± 1.0 mol/L in animals treated with 100 μmol/(h·kg) GSH but did not raise levels of untreated controls (1.8 ± 0.5 mol/L) following infusion of 50 μmol GSH/(h·kg) (2.2 ± 0.2 mol/L).
CONCLUSION: Plasma GSH levels above a critical level may act as a “sink” for ROS produced in the hepatic vasculature during reperfusion of liver grafts. Therefore, GSH can be considered a candidate antioxidant for the prevention of reperfusion injury after liver transplantation, in particular since it has a low toxicity in humans.
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Affiliation(s)
- Rolf J Schauer
- Surgical Department, University Hospital Klinikum Grosshadern, Marchioninistr. 15, 81377 Munich, Germany.
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