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Delligatti CE, Kirk JA. Glycation in the cardiomyocyte. VITAMINS AND HORMONES 2024; 125:47-88. [PMID: 38997172 PMCID: PMC11578284 DOI: 10.1016/bs.vh.2024.04.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/14/2024]
Abstract
Glycation is a protein post-translational modification that can occur on lysine and arginine residues as a result of a non-enzymatic process known as the Maillard reaction. This modification is irreversible, so the only way it can be removed is by protein degradation and replacement. Small reactive carbonyl species, glyoxal and methylglyoxal, are the primary glycating agents and are elevated in several conditions associated with an increased risk of cardiovascular disease, including diabetes, rheumatoid arthritis, smoking, and aging. Thus, how protein glycation impacts the cardiomyocyte is of particular interest, to both understand how these conditions increase the risk of cardiovascular disease and how glycation might be targeted therapeutically. Glycation can affect the cardiomyocyte through extracellular mechanisms, including RAGE-based signaling, glycation of the extracellular matrix that modifies the mechanical environment, and signaling from the vasculature. Intracellular glycation of the cardiomyocyte can impact calcium handling, protein quality control and cell death pathways, as well as the cytoskeleton, resulting in a blunted contractility. While reducing protein glycation and its impact on the heart has been an active area of drug development, multiple clinical trials have had mixed results and these compounds have not been translated to the clinic-highlighting the challenges of modulating myocyte glycation. Here we will review protein glycation and its effects on the cardiomyocyte, therapeutic attempts to reverse these, and offer insight as to the future of glycation studies and patient treatment.
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Affiliation(s)
- Christine E Delligatti
- Department of Cell and Molecular Physiology, Loyola University Chicago Stritch School of Medicine, Maywood, IL, United States
| | - Jonathan A Kirk
- Department of Cell and Molecular Physiology, Loyola University Chicago Stritch School of Medicine, Maywood, IL, United States.
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Conroy LJ, McCann A, Zhang N, de Gaetano M. The role of nanosystems in the delivery of glucose-lowering drugs for the preemption and treatment of diabetes-associated atherosclerosis. Am J Physiol Cell Physiol 2024; 326:C1398-C1409. [PMID: 38525540 DOI: 10.1152/ajpcell.00695.2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Revised: 03/19/2024] [Accepted: 03/19/2024] [Indexed: 03/26/2024]
Abstract
Diabetes is one of the most prevalent diseases worldwide. In recent decades, type-2 diabetes has become increasingly common, particularly in younger individuals. Diabetes leads to many vascular complications, including atherosclerosis. Atherosclerosis is a cardiovascular disease characterized by lipid-rich plaques within the vasculature. Plaques develop over time, restricting blood flow, and can, therefore, be the underlying cause of major adverse cardiovascular events, including myocardial infarction and stroke. Diabetes and atherosclerosis are intrinsically linked. Diabetes is a metabolic syndrome that accelerates atherosclerosis and increases the risk of developing other comorbidities, such as diabetes-associated atherosclerosis (DAA). Gold standard antidiabetic medications focus on attenuating hyperglycemia. Though recent evidence suggests that glucose-lowering drugs may have broader applications, beyond diabetes management. This review mainly evaluates the role of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as liraglutide and semaglutide in DAA. These drugs mimic gut hormones (incretins), which inhibit glucagon secretion while stimulating insulin secretion, thus improving insulin sensitivity. This facilitates delayed gastric emptying and increased patient satiety; hence, they are also indicated for the treatment of obesity. GLP-1 RAs have significant cardioprotective effects, including decreasing low-density lipoprotein (LDL) cholesterol and triglycerides levels. Liraglutide and semaglutide have specifically been shown to decrease cardiovascular risk. Liraglutide has displayed a myriad of antiatherosclerotic properties, with the potential to induce plaque regression. This review aims to address how glucose-lowering medications can be applied to treat diseases other than diabetes. We specifically focus on how nanomedicines can be used for the site-specific delivery of antidiabetic medicines for the treatment of diabetes-associated atherosclerosis.
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Affiliation(s)
- Luke James Conroy
- Diabetes Complications Research Centre, Conway Institute & School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland
| | - Alyssa McCann
- School of Mechanical and Materials Engineering, University College Dublin, Dublin, Ireland
| | - Nan Zhang
- School of Mechanical and Materials Engineering, University College Dublin, Dublin, Ireland
| | - Monica de Gaetano
- Diabetes Complications Research Centre, Conway Institute & School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland
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Uceda AB, Mariño L, Casasnovas R, Adrover M. An overview on glycation: molecular mechanisms, impact on proteins, pathogenesis, and inhibition. Biophys Rev 2024; 16:189-218. [PMID: 38737201 PMCID: PMC11078917 DOI: 10.1007/s12551-024-01188-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/21/2024] [Indexed: 05/14/2024] Open
Abstract
The formation of a heterogeneous set of advanced glycation end products (AGEs) is the final outcome of a non-enzymatic process that occurs in vivo on long-life biomolecules. This process, known as glycation, starts with the reaction between reducing sugars, or their autoxidation products, with the amino groups of proteins, DNA, or lipids, thus gaining relevance under hyperglycemic conditions. Once AGEs are formed, they might affect the biological function of the biomacromolecule and, therefore, induce the development of pathophysiological events. In fact, the accumulation of AGEs has been pointed as a triggering factor of obesity, diabetes-related diseases, coronary artery disease, neurological disorders, or chronic renal failure, among others. Given the deleterious consequences of glycation, evolution has designed endogenous mechanisms to undo glycation or to prevent it. In addition, many exogenous molecules have also emerged as powerful glycation inhibitors. This review aims to provide an overview on what glycation is. It starts by explaining the similarities and differences between glycation and glycosylation. Then, it describes in detail the molecular mechanism underlying glycation reactions, and the bio-molecular targets with higher propensity to be glycated. Next, it discusses the precise effects of glycation on protein structure, function, and aggregation, and how computational chemistry has provided insights on these aspects. Finally, it reports the most prevalent diseases induced by glycation, and the endogenous mechanisms and the current therapeutic interventions against it.
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Affiliation(s)
- Ana Belén Uceda
- Departament de Química, Universitat de Les Illes Balears, Health Research Institute of the Balearic Islands (IdISBa), Ctra. Valldemossa Km 7.5, 07122 Palma, Spain
| | - Laura Mariño
- Departament de Química, Universitat de Les Illes Balears, Health Research Institute of the Balearic Islands (IdISBa), Ctra. Valldemossa Km 7.5, 07122 Palma, Spain
| | - Rodrigo Casasnovas
- Departament de Química, Universitat de Les Illes Balears, Health Research Institute of the Balearic Islands (IdISBa), Ctra. Valldemossa Km 7.5, 07122 Palma, Spain
| | - Miquel Adrover
- Departament de Química, Universitat de Les Illes Balears, Health Research Institute of the Balearic Islands (IdISBa), Ctra. Valldemossa Km 7.5, 07122 Palma, Spain
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Fernandes SA, Dasgupta S, Tupe RS, Pathan EK. Structure-guided approach to modify the substrate specificity of the protein human deglycase-1 (hDJ-1). Biochem Biophys Res Commun 2023; 679:122-128. [PMID: 37688845 DOI: 10.1016/j.bbrc.2023.08.058] [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: 08/14/2023] [Accepted: 08/26/2023] [Indexed: 09/11/2023]
Abstract
Glycation is a non-enzymatic reaction wherein sugars or dicarbonyls such as methylglyoxal (MGO) and glyoxal (GO) react with proteins, leading to protein inactivation. The hydrolysing enzyme human deglycase-1 (hDJ-1) is reported to decrease glycative stress by deglycating the modified proteins, specifically at cysteine, lysine, and arginine sites. This specificity of hDJ-1 is thought to be regulated by its active site cysteine residue (Cys106). Structural analysis of hDJ-1 by molecular docking and simulation studies, however, indicates a possible role of glutamate (Glu18) in determining its substrate specificity. To elucidate this, Glu18 present at the catalytic site of hDJ-1 was modified to aspartate (Asp18) by SDM, and the resultant mutant was termed mutant DJ-1 (mDJ-1). Both hDJ-1 and mDJ-1 were heterologously expressed in Escherichia coli BL21 (DE3) strain and purified to homogeneity. The hDJ-1 showed kcat values of 1.45 × 103 s-1, 3.6 × 102 s-1, and 3.1 × 102 s-1, and Km values 0.181 mM, 18.18 mM, and 12.5 mM for N-acetylcysteine (NacCys), N-acetyllysine (NacLys), and N-acetylarginine (NacArg), respectively. The mDJ-1 showed altered kcat values (8 × 102 s-1, 3.8 × 102 s-1, 4.9 × 102 s-1) and Km values of 0.14 mM, 6.25 mM, 5.88 mM for NacCys, NacLys and NacArg, respectively. A single amino acid change (Glu18 to Asp18) improved the substrate specificity of mDJ-1 toward NacLys and NacArg. Understanding hDJ-1's structure and enhanced functionality will facilitate further exploration of its therapeutic potential for the treatment of glycation-induced diabetic complications.
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Affiliation(s)
- Sera A Fernandes
- Symbiosis School of Biological Sciences, Symbiosis International (Deemed University), Lavale, Pune, 412115, Maharashtra, India
| | - Subrata Dasgupta
- Department of Bioscience and Bioengineering, Indian Institute of Technology (IIT), Bombay, Powai, Mumbai, 400076, Maharashtra, India
| | - Rashmi S Tupe
- Symbiosis School of Biological Sciences, Symbiosis International (Deemed University), Lavale, Pune, 412115, Maharashtra, India.
| | - Ejaj K Pathan
- Symbiosis School of Biological Sciences, Symbiosis International (Deemed University), Lavale, Pune, 412115, Maharashtra, India.
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Wölk M, Prabutzki P, Fedorova M. Analytical Toolbox to Unlock the Diversity of Oxidized Lipids. Acc Chem Res 2023; 56:835-845. [PMID: 36943749 DOI: 10.1021/acs.accounts.2c00842] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/23/2023]
Abstract
ConspectusLipids are diverse class of small biomolecules represented by a large variety of chemical structures. In addition to the classical biosynthetic routes, lipids can undergo numerous modifications via introduction of small chemical moieties forming hydroxyl, phospho, and nitro derivatives, among others. Such modifications change the physicochemical properties of a parent lipid and usually result in new functionalities either by mediating signaling events or by changing the biophysical properties of lipid membranes. Over the last decades, a large body of evidence indicated the involvement of lipid modifications in a variety of physiological and pathological events. For instance, lipid (per)oxidation for a long time was considered as a hallmark of oxidative stress and related proinflammatory signaling. Recently, however, with the burst in the development of the redox biology field, oxidative modifications of lipids are also recognized as a part of regulatory and adaptive events that are highly specific for particular cell types, tissues, and conditions.The initial diversity of lipid species and the variety of possible lipid modifications result in an extremely large chemical space of the epilipidome, the subset of the natural lipidome formed by enzymatic and non-enzymatic lipid modifications occurring in biological systems. Together with their low natural abundance, structural annotation of modified lipids represents a major analytical challenge limiting the discovery of their natural variety and functions. Furthermore, the number of available chemically characterized standards representing various modified lipid species remains limited, making analytical and functional studies very challenging. Over the past decade we have developed and implemented numerous analytical methods to study lipid modifications and applied them in the context of different biological conditions. In this Account, we outline the development and evolution of modern mass-spectrometry-based techniques for the structural elucidation of modified/oxidized lipids and corresponding applications. Research of our group is mostly focused on redox biology, and thus, our primary interest was always the analysis of lipid modifications introduced by redox disbalance, including lipid peroxidation (LPO), oxygenation, nitration, and glycation. To this end, we developed an array of analytical solutions to measure carbonyls derived from LPO, oxidized and nitrated fatty acid derivatives, and oxidized and glycated complex lipids. We will briefly describe the main analytical challenges along with corresponding solutions developed by our group toward deciphering the complexity of natural epilipdomes, starting from in vitro-oxidized lipid mixtures, artificial membranes, and lipid droplets, to illustrate the diversity of lipid modifications in the context of metabolic diseases and ferroptotic cell death.
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Affiliation(s)
- Michele Wölk
- Center of Membrane Biochemistry and Lipid Research, Faculty of Medicine Carl Gustav Carus of TU Dresden, 01307 Dresden, Germany
| | - Patricia Prabutzki
- Institute for Medical Physics and Biophysics, Faculty of Medicine, Leipzig University, 04107 Leipzig, Germany
| | - Maria Fedorova
- Center of Membrane Biochemistry and Lipid Research, Faculty of Medicine Carl Gustav Carus of TU Dresden, 01307 Dresden, Germany
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Lipoxin and glycation in SREBP signaling: Insight into diabetic cardiomyopathy and associated lipotoxicity. Prostaglandins Other Lipid Mediat 2023; 164:106698. [PMID: 36379414 DOI: 10.1016/j.prostaglandins.2022.106698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 11/08/2022] [Accepted: 11/10/2022] [Indexed: 11/15/2022]
Abstract
Diabetes and cardiovascular diseases are the leading cause of morbidity and mortality worldwide. Diabetes increases cardiovascular risk through hyperglycemia and atherosclerosis. Chronic hyperglycemia accelerates glycation reaction, which forms advanced glycation end products (AGEs). Additionally, hyperglycemia with enhanced levels of cholesterol, native and oxidized low-density lipoproteins, free fatty acids, and oxidative stress induces lipotoxicity. Accelerated glycation and disturbed lipid metabolism are characteristic features of diabetic heart failure. SREBP signaling plays a significant role in lipid and glucose homeostasis. AGEs increase lipotoxicity in diabetic cardiomyopathy by inhibiting SREBP signaling. While anti-inflammatory lipid mediators, lipoxins resolve inflammation caused by lipotoxicity by upregulating the PPARγ expression and regulating CD36. PPARγ connects the bridge between glycation and lipoxin in SREBP signaling. A summary of treatment modalities against diabetic cardiomyopathy is given in brief. This review indicates the novel therapeutic approach in the crosstalk between glycation and lipoxin in SREBP signaling.
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Pero ME, Chowdhury F, Bartolini F. Role of tubulin post-translational modifications in peripheral neuropathy. Exp Neurol 2023; 360:114274. [PMID: 36379274 PMCID: PMC11320756 DOI: 10.1016/j.expneurol.2022.114274] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Revised: 11/06/2022] [Accepted: 11/08/2022] [Indexed: 11/14/2022]
Abstract
Peripheral neuropathy is a common disorder that results from nerve damage in the periphery. The degeneration of sensory axon terminals leads to changes or loss of sensory functions, often manifesting as debilitating pain, weakness, numbness, tingling, and disability. The pathogenesis of most peripheral neuropathies remains to be fully elucidated. Cumulative evidence from both early and recent studies indicates that tubulin damage may provide a common underlying mechanism of axonal injury in various peripheral neuropathies. In particular, tubulin post-translational modifications have been recently implicated in both toxic and inherited forms of peripheral neuropathy through regulation of axonal transport and mitochondria dynamics. This knowledge forms a new area of investigation with the potential for developing therapeutic strategies to prevent or delay peripheral neuropathy by restoring tubulin homeostasis.
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Affiliation(s)
- Maria Elena Pero
- Department of Pathology and Cell Biology, Columbia University, New York, USA; Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Italy
| | - Farihah Chowdhury
- Department of Pathology and Cell Biology, Columbia University, New York, USA
| | - Francesca Bartolini
- Department of Pathology and Cell Biology, Columbia University, New York, USA.
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Abstract
The traditional complications of diabetes mellitus are well known and continue to pose a considerable burden on millions of people living with diabetes mellitus. However, advances in the management of diabetes mellitus and, consequently, longer life expectancies, have resulted in the emergence of evidence of the existence of a different set of lesser-acknowledged diabetes mellitus complications. With declining mortality from vascular disease, which once accounted for more than 50% of deaths amongst people with diabetes mellitus, cancer and dementia now comprise the leading causes of death in people with diabetes mellitus in some countries or regions. Additionally, studies have demonstrated notable links between diabetes mellitus and a broad range of comorbidities, including cognitive decline, functional disability, affective disorders, obstructive sleep apnoea and liver disease, and have refined our understanding of the association between diabetes mellitus and infection. However, no published review currently synthesizes this evidence to provide an in-depth discussion of the burden and risks of these emerging complications. This Review summarizes information from systematic reviews and major cohort studies regarding emerging complications of type 1 and type 2 diabetes mellitus to identify and quantify associations, highlight gaps and discrepancies in the evidence, and consider implications for the future management of diabetes mellitus.
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Affiliation(s)
- Dunya Tomic
- Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
| | - Jonathan E Shaw
- Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
| | - Dianna J Magliano
- Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
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Chen L, Xu R, McDonald JD, Bruno RS, Choueiry F, Zhu J. Dairy Milk Casein and Whey Proteins Differentially Alter the Postprandial Lipidome in Persons with Prediabetes: A Comparative Lipidomics Study. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2022; 70:10209-10220. [PMID: 35948437 PMCID: PMC10352119 DOI: 10.1021/acs.jafc.2c03662] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Dairy milk, likely through its bioactive proteins, has been reported to attenuate postprandial hyperglycemia-induced oxidative stress responses implicated in cardiovascular diseases (CVDs). However, how its major proteins, whey and casein, alter metabolic excursions of the lipidome in persons with prediabetes is unclear. Therefore, the objective of this study was to examine whey or casein protein ingestion on glucose-induced alternations in lipidomic responses in adults (17 males and 6 females) with prediabetes. In this clinical study, participants consumed glucose alone, glucose + nonfat milk (NFM), or glucose with either whey (WHEY) or casein (CASEIN) protein, and plasma samples were collected at multiple time points. Lipidomics data from plasma samples was acquired using an ultra-high-performance liquid chromatography-high-resolution mass spectrometry-based platform. Our results indicated that glucose ingestion alone induced the largest number of changes in plasma lipids. WHEY showed an earlier and stronger impact to maintain the stability of the lipidome compared with CASEIN. WHEY protected against glucose-induced changes in glycerophospholipid and sphingolipid (SP) metabolism, while ether lipid metabolism and SP metabolism were the pathways most greatly impacted in CASEIN. Meanwhile, the decreased acyl carnitines and fatty acid (FA) 16:0 levels could attenuate lipid peroxidation after protein intervention to protect insulin secretory capacity. Diabetes-associated lipids, the increased phosphatidylethanolamine (PE) 34:2 and decreased phosphatidylcholine (PC) 34:3 in the NFM-T90 min, elevated PC 35:4 and decreased CE 18:1 to a CE 18:2 ratio in the WHEY-T180 min, decreased lysophosphatidylcholine (LPC) 22:6 and LPC 22:0/0:0 in the CASEIN-T90 min, and decreased PE 36:1 in the CASEIN-T180 min, indicating a decreased risk for prediabetes. Collectively, our study suggested that dairy milk proteins are responsible for the protective effect of non-fat milk on glucose-induced changes in the lipidome, which may potentially influence long-term CVD risk.
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Affiliation(s)
- Li Chen
- Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA
- James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA
| | - Rui Xu
- Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA
| | - Joshua D. McDonald
- Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA
| | - Richard S. Bruno
- Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA
| | - Fouad Choueiry
- Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA
| | - Jiangjiang Zhu
- Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA
- James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA
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Engel C, Meade R, Harroun N, Penrose A, Shafqat M, Jin X, DeSilva G, Semenkovich C, Zayed M. Altered Peroxisome Proliferator-Activated Receptor Alpha Signaling in Variably Diseased Peripheral Arterial Segments. Front Cardiovasc Med 2022; 9:834199. [PMID: 35783870 PMCID: PMC9248745 DOI: 10.3389/fcvm.2022.834199] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Accepted: 05/04/2022] [Indexed: 11/25/2022] Open
Abstract
Objective Peripheral atherosclerosis that accumulates in the extracranial carotid and lower extremity arteries can lead to significant morbidity and mortality. However, atherosclerotic disease progression is often not homogenous and is accelerated by diabetes. We previously observed increased phospholipid content in minimally (Min)-diseased arterial segments compared to maximally (Max)-diseased segments. Since Peroxisome Proliferator-Activated Receptor alpha (PPARα) is a key regulator of lipid metabolism, we hypothesized that it may have differential expression and signaling in Min vs. Max-diseased peripheral arterial segments. Methods Eighteen patients who underwent carotid endarterectomy (CEA), and 34 patients who underwent major lower extremity amputation were prospectively enrolled into a vascular tissue biobank. Min and Max-diseased segments were obtained in real-time from CEA plaque and amputated lower extremity arterial segments. mRNA and protein were isolated from specimens and the relative expression of ppara, and its downstream genes Acyl-CoA Oxidase 1 (acox1) and Carnitine Palmitoyltransferase 1A (cpt1a) were also evaluated. We evaluated gene expression and protein content relative to atherosclerotic disease severity and clinical diabetes status. Gene expression was also evaluated relative to Hemoglobin A1c and serum lipid profiles. Results In CEA segments of patients with diabetes, we observed significantly higher ppara and acox1 gene expression (p < 0.01 and p < 0.001 respectively), and higher PPARα protein content (p < 0.05). Hemoglobin A1c significantly correlated with expression of ppara (R2 = 0.66, p < 0.001), acox1 (R2 = 0.31, p < 0.05), and cpt1a (R2 = 0.4, p < 0.05). There was no significant difference in gene expression between Min vs. Max-diseased CEA plaque segments. Conversely, in lower extremity arterial segments of patients with diabetes, we observed significantly lower ppara, acox1, and cpt1a expression (p < 0.05, p < 0.001, and p < 0.0001 respectively). Interestingly, CPT1A content was lower in arterial segments of patients with diabetes (p < 0.05). Hemoglobin A1c and HDL-cholesterol had negative correlations with ppara (R2 = 0.44, p < 0.05; R2 = 0.42, p < 0.05; respectively). Conclusion This study demonstrates the significant differential expression of ppara and its immediate downstream genes in human carotid and lower extremity arteries relative to disease severity and diabetes. These findings highlight that mechanisms that influence atheroprogression in the carotid and lower extremities peripheral arteries are not homogenous and can be impacted by patient diabetes status and serum cholesterol profiles. Further elucidating these differential molecular mechanisms can help improve targeted therapy of atherosclerosis in different peripheral arterial beds.
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Affiliation(s)
- Connor Engel
- Section of Vascular Surgery, Department of Surgery, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
| | - Rodrigo Meade
- Section of Vascular Surgery, Department of Surgery, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
| | - Nikolai Harroun
- Section of Vascular Surgery, Department of Surgery, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
| | - Amanda Penrose
- Section of Vascular Surgery, Department of Surgery, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
| | - Mehreen Shafqat
- Section of Vascular Surgery, Department of Surgery, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
| | - Xiaohua Jin
- Section of Vascular Surgery, Department of Surgery, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
| | - Gayan DeSilva
- Section of Vascular Surgery, Department of Surgery, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
| | - Clay Semenkovich
- Division of Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
| | - Mohamed Zayed
- Section of Vascular Surgery, Department of Surgery, Washington University in St. Louis School of Medicine, St. Louis, MO, United States,Division of Molecular Cell Biology, Washington University in St. Louis School of Medicine, St. Louis, MO, United States,Department of Biomedical Engineering, McKelvey School of Engineering, Washington University in St. Louis, St. Louis, MO, United States,Veterans Affairs St. Louis Health Care System, St. Louis, MO, United States,*Correspondence: Mohamed Zayed,
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11
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Reyes-Pardo H, Sánchez-Herrera DP, Santillan M. On the effects of diabetes mellitus on the mechanical properties of DRG sensory neurons and their possible relation with diabetic neuropathy. Phys Biol 2022; 19. [PMID: 35417901 DOI: 10.1088/1478-3975/ac6722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Accepted: 04/13/2022] [Indexed: 11/12/2022]
Abstract
Diabetic neuropathy (DN) is one of the principal complications of diabetes mellitus (DM). Dorsal root ganglion (DRG) neurons are the primary sensory neurons that transduce mechanical, chemical, thermal, and pain stimuli. Diabetes-caused sensitivity alterations and presence of pain are due to cellular damage originated by persistent hyperglycemia, microvascular insufficiency, and oxidative and nitrosative stress. However, the underlying mechanisms have not been fully clarified. The present work addresses this problem by hypothesizing that sensitivity changes in DN result from mechanotransduction-system alterations in sensory neurons; especially, plasma membrane affectations. This hypothesis is tackled by means of elastic-deformation experiments performed on DGR neurons from a murine model for type-1 DM, as well a mathematical model of the cell mechanical structure. The obtained results suggest that the plasma-membrane fluidity of DRG sensory neurons is modified by the induction of DM, and that this alteration may correlate with changes in the cell calcium transient that results from mechanical stimuli.
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Affiliation(s)
- Humberto Reyes-Pardo
- School of Engineering and Sciences, Tecnologico de Monterrey, Av. Eugenio Garza Sada, Monterrey, Nuevo Leon, 64849, MEXICO
| | - Daniel P Sánchez-Herrera
- Via del Conocimiento 201, Centro de Investigación y de Estudios Avanzados Unidad Monterrey, Parque PIIT, Apodaca, Nuevo León, 66628, MEXICO
| | - Moises Santillan
- Via del Conocimiento 201, Centro de Investigación y de Estudios Avanzados Unidad Monterrey, Parque PIIT, Apodaca, Nuevo León, 66628, MEXICO
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12
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Park SY, Suh KS, Jung WW, Chin SO. Spironolactone Attenuates Methylglyoxal-induced Cellular Dysfunction in MC3T3-E1 Osteoblastic Cells. J Korean Med Sci 2021; 36:e265. [PMID: 34609092 PMCID: PMC8490790 DOI: 10.3346/jkms.2021.36.e265] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Accepted: 08/29/2021] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Methylglyoxal (MG) is associated with the pathogenesis of age- and diabetes-related complications. Spironolactone is a competitive antagonist of aldosterone that is widely employed in the treatment of hypertension and heart failure. This study examined the effects of spironolactone on MG-induced cellular dysfunction in MC3T3-E1 osteoblastic cells. METHODS MC3T3-E1 cells were treated with spironolactone in the presence of MG. The mitochondrial function, bone formation activity, oxidative damage, inflammatory cytokines, glyoxalase I activity, and glutathione (GSH) were measured. RESULTS Pretreatment of MC3T3-E1 osteoblastic cells with spironolactone prevented MG-induced cell death, and improved bone formation activity. Spironolactone reduced MG-induced endoplasmic reticulum stress, production of intracellular reactive oxygen species, mitochondrial superoxides, cardiolipin peroxidation, and inflammatory cytokines. Pretreatment with spironolactone also increased the level of reduced GSH and the activity of glyoxalase I. MG induced mitochondrial dysfunction, but markers of mitochondrial biogenesis such as mitochondrial membrane potential, adenosine triphosphate, proliferator-activated receptor gamma coactivator 1α, and nitric oxide were significantly improved by treatment of spironolactone. CONCLUSION Spironolactone could prevent MG-induced cytotoxicity in MC3T3-E1 osteoblastic cells by reduction of oxidative stress. The oxidative stress reduction was explained by spironolactone's inhibition of advanced glycation end-product formation, restoring mitochondrial dysfunction, and anti-inflammatory effect.
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Affiliation(s)
- So Young Park
- Department of Endocrinology and Metabolism, Kyung Hee University Hospital, Seoul, Korea
| | - Kwang Sik Suh
- Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine, Seoul, Korea
| | - Woon-Won Jung
- Department of Biomedical Laboratory Science, College of Health and Medical Sciences, Cheongju University, Cheongju, Korea
| | - Sang Ouk Chin
- Department of Endocrinology and Metabolism, Kyung Hee University Hospital, Seoul, Korea
- Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine, Seoul, Korea.
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13
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Pantner Y, Polavarapu R, Chin LS, Li L, Shimizu Y, Calvert JW. DJ-1 attenuates the glycation of mitochondrial complex I and complex III in the post-ischemic heart. Sci Rep 2021; 11:19408. [PMID: 34593886 PMCID: PMC8484662 DOI: 10.1038/s41598-021-98722-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Accepted: 09/09/2021] [Indexed: 02/02/2023] Open
Abstract
DJ-1 is a ubiquitously expressed protein that protects cells from stress through its conversion into an active protease. Recent work found that the active form of DJ-1 was induced in the ischemic heart as an endogenous mechanism to attenuate glycative stress-the non-enzymatic glycosylation of proteins. However, specific proteins protected from glycative stress by DJ-1 are not known. Given that mitochondrial electron transport proteins have a propensity for being targets of glycative stress, we investigated if DJ-1 regulates the glycation of Complex I and Complex III after myocardial ischemia-reperfusion (I/R) injury. Initial studies found that DJ-1 localized to the mitochondria and increased its interaction with Complex I and Complex III 3 days after the onset of myocardial I/R injury. Next, we investigated the role DJ-1 plays in modulating glycative stress in the mitochondria. Analysis revealed that compared to wild-type control mice, mitochondria from DJ-1 deficient (DJ-1 KO) hearts showed increased levels of glycative stress following I/R. Additionally, Complex I and Complex III glycation were found to be at higher levels in DJ-1 KO hearts. This corresponded with reduced complex activities, as well as reduced mitochondrial oxygen consumption ant ATP synthesis in the presence of pyruvate and malate. To further determine if DJ-1 influenced the glycation of the complexes, an adenoviral approach was used to over-express the active form of DJ-1(AAV9-DJ1ΔC). Under I/R conditions, the glycation of Complex I and Complex III were attenuated in hearts treated with AAV9-DJ1ΔC. This was accompanied by improvements in complex activities, oxygen consumption, and ATP production. Together, this data suggests that cardiac DJ-1 maintains Complex I and Complex III efficiency and mitochondrial function during the recovery from I/R injury. In elucidating a specific mechanism for DJ-1's role in the post-ischemic heart, these data break new ground for potential therapeutic strategies using DJ-1 as a target.
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Affiliation(s)
- Yvanna Pantner
- Department of Surgery, Division of Cardiothoracic Surgery, Carlyle Fraser Heart Center, Emory University School of Medicine, 101 Woodruff Circle, Atlanta, GA, 30322, USA
| | - Rohini Polavarapu
- Department of Surgery, Division of Cardiothoracic Surgery, Carlyle Fraser Heart Center, Emory University School of Medicine, 101 Woodruff Circle, Atlanta, GA, 30322, USA
| | - Lih-Shen Chin
- Department Pharmacology, Emory University School of Medicine, Atlanta, GA, USA
| | - Lian Li
- Department Pharmacology, Emory University School of Medicine, Atlanta, GA, USA
| | - Yuuki Shimizu
- Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan
| | - John W Calvert
- Department of Surgery, Division of Cardiothoracic Surgery, Carlyle Fraser Heart Center, Emory University School of Medicine, 101 Woodruff Circle, Atlanta, GA, 30322, USA.
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14
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Khanam A, Ahmad S, Husain A, Rehman S, Farooqui A, Yusuf MA. Glycation and Antioxidants: Hand in the Glove of Antiglycation and Natural Antioxidants. Curr Protein Pept Sci 2021; 21:899-915. [PMID: 32039678 DOI: 10.2174/1389203721666200210103304] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Revised: 09/09/2019] [Accepted: 11/30/2019] [Indexed: 12/17/2022]
Abstract
The non-enzymatic interaction of sugar and protein resulting in the formation of advanced glycation end products responsible for cell signaling alterations ultimately leads to the human chronic disorders such as diabetes mellitus, cardiovascular diseases, cancer, etc. Studies suggest that AGEs upon interaction with receptors for advanced glycation end products (RAGE) result in the production of pro-inflammatory molecules and free radicals that exert altered gene expression effect. To date, many studies unveiled the potent role of synthetic and natural agents in inhibiting the glycation reaction at a lesser or greater extent. This review focuses on the hazards of glycation reaction and its inhibition by natural antioxidants, including polyphenols.
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Affiliation(s)
- Afreen Khanam
- IIRC-1, Laboratory of Glycation Biology and Metabolic Disorders, Integral University, Lucknow, India
| | - Saheem Ahmad
- IIRC-1, Laboratory of Glycation Biology and Metabolic Disorders, Integral University, Lucknow, India
| | - Arbab Husain
- IIRC-1, Laboratory of Glycation Biology and Metabolic Disorders, Integral University, Lucknow, India
| | - Shahnawaz Rehman
- IIRC-1, Laboratory of Glycation Biology and Metabolic Disorders, Integral University, Lucknow, India
| | - Alvina Farooqui
- Department of Bioengineering, Integral University, Lucknow, India
| | - Mohd Aslam Yusuf
- Department of Bioengineering, Integral University, Lucknow, India
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15
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Frolova N, Soboleva A, Nguyen VD, Kim A, Ihling C, Eisenschmidt-Bönn D, Mamontova T, Herfurth UM, Wessjohann LA, Sinz A, Birkemeyer C, Frolov A. Probing glycation potential of dietary sugars in human blood by an integrated in vitro approach. Food Chem 2020; 347:128951. [PMID: 33493836 DOI: 10.1016/j.foodchem.2020.128951] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Revised: 12/11/2020] [Accepted: 12/22/2020] [Indexed: 01/12/2023]
Abstract
Glycation is referred to as the interaction of protein amino and guanidino groups with reducing sugars and carbonyl products of their degradation. Resulting advanced glycation end-products (AGEs) contribute to pathogenesis of diabetes mellitus and neurodegenerative disorders. Upon their intestinal absorption, dietary sugars and α-dicarbonyl compounds interact with blood proteins yielding AGEs. Although the differences in glycation potential of monosaccharides are well characterized, the underlying mechanisms are poorly understood. To address this question, d-glucose, d-fructose and l-ascorbic acid were incubated with human serum albumin (HSA). The sugars and α-dicarbonyl intermediates of their degradation were analyzed in parallel to protein glycation patterns (exemplified with hydroimidazolone modifications of arginine residues and products of their hydrolysis) by bottom-up proteomics and computational chemistry. Glycation of HSA with sugars revealed 9 glyoxal- and 14 methylglyoxal-derived modification sites. Their dynamics was sugar-specific and depended on concentrations of α-dicarbonyls, their formation kinetics, and presence of stabilizing residues in close proximity to the glycation sites.
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Affiliation(s)
- Nadezhda Frolova
- Institute of Analytical Chemistry, Faculty of Chemistry and Mineralogy, University of Leipzig, Germany
| | - Alena Soboleva
- Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Germany; Department of Biochemistry, St. Petersburg State University, Russia.
| | - Viet Duc Nguyen
- Institute of Analytical Chemistry, Faculty of Chemistry and Mineralogy, University of Leipzig, Germany; Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Germany
| | - Ahyoung Kim
- Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Germany
| | - Christian Ihling
- Department of Pharmaceutical Chemistry and Bioanalytics, Institute of Pharmacy, Martin-Luther Universität Halle-Wittenberg, Germany
| | | | - Tatiana Mamontova
- Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Germany; Department of Biochemistry, St. Petersburg State University, Russia
| | - Uta M Herfurth
- Department of Food Safety, German Federal Institute for Risk Assessment, Germany
| | - Ludger A Wessjohann
- Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Germany
| | - Andrea Sinz
- Department of Pharmaceutical Chemistry and Bioanalytics, Institute of Pharmacy, Martin-Luther Universität Halle-Wittenberg, Germany
| | - Claudia Birkemeyer
- Institute of Analytical Chemistry, Faculty of Chemistry and Mineralogy, University of Leipzig, Germany
| | - Andrej Frolov
- Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Germany; Department of Biochemistry, St. Petersburg State University, Russia.
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16
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Assessment of Absorption of Glycated Nail Proteins in Patients with Diabetes Mellitus and Diabetic Retinopathy. ACTA ACUST UNITED AC 2020; 56:medicina56120658. [PMID: 33260342 PMCID: PMC7760767 DOI: 10.3390/medicina56120658] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 11/17/2020] [Accepted: 11/27/2020] [Indexed: 12/12/2022]
Abstract
Background and objectives: Glycation occurs in a variety of human tissues and organs. Knowledge about the relationship between predictive biochemical factors such as absorption of glycated nail proteins and severity of type 2 diabetes mellitus (DM) and diabetic retinopathy (DR) remains limited. Materials and Methods: The study group consisted of patients with type 2 DM and DR (n = 32) and a control group (n = 28). Each patient underwent a comprehensive ophthalmic examination. The glycation process in nail clippings was evaluated in stages of in vitro glycation and deglycation stages. ATR–FTIR spectroscopy was used to calculate the infrared absorption in the region of interest. The absorption of solutions with nail clippings was evaluated by NanoDrop spectrophotometry. Absorption spectra differences before and after the exposure to fructosamine 3-kinase were compared between DM patients with DR and the control group. Results: The absorption of glycated nail protein greater than 83.00% increased the chance of developing DM and DR (OR = 15.909, 95% CI 3.914–64.660, p < 0.001). Absorption of glycated nail protein by ATR–FTIR spectroscopy in patients with DM and DR in vitro glycation was statistically significantly higher than in the control group; also absorption of solution with nails by NanoDrop spectroscopy was statistically significantly higher than in controls in vitro glycation and in vitro deglycation. After exposure to fructosamine 3-kinase, absorption of nail protein in DM + severe/proliferative DR group was statistically significantly lower in comparison with DM + mild/moderate group DR. Conclusions: Evaluation of glycated nail protein could be applied to evaluate the risk of having DM and for long-term observation of DM control.
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17
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A UPLC-MRM-MS method for comprehensive profiling of Amadori compound-modified phosphatidylethanolamines in human plasma. Anal Bioanal Chem 2020; 413:431-443. [PMID: 33111151 DOI: 10.1007/s00216-020-03012-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 09/28/2020] [Accepted: 10/15/2020] [Indexed: 10/23/2022]
Abstract
Phosphatidylethanolamines (PEs) are targets of non-enzymatic glycation, a chemical process that occurs between glucose and primary amine-containing biomolecules. As the early-stage non-enzymatic glycation products of PE, Amadori-PEs are implicated in the pathogenesis of various diseases. However, only a few Amadori-PE molecular species have been identified so far; a comprehensive profiling of these glycated PE species is needed to establish their roles in disease pathology. Herein, based on our previous work using liquid chromatography-coupled neutral loss scanning and product ion scanning tandem mass spectrometry (LC-NLS-MS and LC-PIS-MS) in tandem, we extend identification of Amadori-PE to the low-abundance species, which is facilitated by using plasma lipids glycated in vitro. The confidence of identification is improved by high-resolution tandem mass spectrometry and chromatographic retention time regression. A LC-coupled multiple reaction monitoring mass spectrometry (LC-MRM-MS) assay is further developed for more sensitive quantitation of the Amadori compound-modified lipids. Using synthesized stable isotope-labeled Amadori lipids as internal standards, levels of 142 Amadori-PEs and 33 Amadori-LysoPEs are determined in the NIST human plasma standard reference material. These values may serve as an important reference for future investigations of Amadori-modified lipids in human diseases.
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18
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Li W, Chen C, Chen M, Zhang X, Ji Q, Wang Y, Zheng Q, Tan S, Gao X, Lu Y. Salted and Unsalted Zhàcài (Brassica juncea var. tumida) Alleviated High-Fat Diet-Induced Dyslipidemia by Regulating Gut Microbiota: A Multiomics Study. Mol Nutr Food Res 2020; 64:e2000798. [PMID: 33098239 DOI: 10.1002/mnfr.202000798] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Revised: 09/23/2020] [Indexed: 12/15/2022]
Abstract
SCOPE Zhàcài (ZC), a salting-processed Brassica juncea var. tumida vegetable, is widely consumed as a pickle, but little is known about the health benefits of both salted and unsalted ZC as a whole food. METHODS AND RESULTS The preventive effects of salted and unsalted ZC against dyslipidemia are assessed in high-fat (HF) diet-fed mice. HF intake for 12 continuous weeks cause dyslipidemia in mice, as evidenced by the elevations in serum total triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels by 30%, 66%, and 117%, respectively. Metabolomics analysis and the 16S rRNA genes sequencing suggest that dietary administration of salted and unsalted ZC (2.5% w/w) alleviates HF-induced dyslipidemia, metabolic disorders of short-chain fatty acids, and disturbance of intestinal flora in mice. These positive effects of unsalted ZC are stronger than those of salted ZC. Moreover, fecal bacteria transplantation confirms the antidyslipidemia of ZC. CONCLUSION These results suggest that consumption of ZC may prevent HF-induced dyslipidemia by regulating gut microbiota.
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Affiliation(s)
- Wenfeng Li
- School of Life Science and Biotechnology, Yangtze Normal University, Chongqing, 408100, China
| | - Chunlian Chen
- School of Life Science and Biotechnology, Yangtze Normal University, Chongqing, 408100, China
| | - Mengting Chen
- School of Life Science and Biotechnology, Yangtze Normal University, Chongqing, 408100, China
| | - Xiangyang Zhang
- School of Life Science and Biotechnology, Yangtze Normal University, Chongqing, 408100, China
| | - Qin Ji
- School of Life Science and Biotechnology, Yangtze Normal University, Chongqing, 408100, China
| | - Yu Wang
- School of Life Science and Biotechnology, Yangtze Normal University, Chongqing, 408100, China
| | - Qiaoran Zheng
- School of Life Science and Biotechnology, Yangtze Normal University, Chongqing, 408100, China
| | - Si Tan
- School of Life Science and Biotechnology, Yangtze Normal University, Chongqing, 408100, China
| | - Xiaoxv Gao
- School of Life Science and Biotechnology, Yangtze Normal University, Chongqing, 408100, China
| | - Yalong Lu
- College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an, 710062, China
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19
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Han L, Lin Q, Liu G, Han D, Niu L, Su D. Lipids Promote Glycated Phospholipid Formation by Inducing Hydroxyl Radicals in a Maillard Reaction Model System. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2019; 67:7961-7967. [PMID: 31260294 DOI: 10.1021/acs.jafc.9b02771] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
Food-derived glycated phospholipids is potentially hazardous to human health. However, there are few studies on the effects of lipids on the formation of glycated phospholipids. In this work, two model systems were established: (1) a model system including 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (PE), glucose, and Fenton reagent and (2) a model system including PE, glucose, and five kind of vegetable oils. The contents of carboxymethyl-PE, carboxyethyl-PE, Amadori-PE, hydroxyl radical (OH•), glyoxal, and methylglyoxal were determined with high-performance liquid chromatography mass spectrometry. The results of the first model system showed that OH• oxidized glucose to produce glyoxal and methylglyoxal, which then reacted with PE to form carboxymethyl-PE and carboxyethyl-PE. OH• also oxidized Amadori-PE to form carboxymethyl-PE. The results of the second model system showed that vegetable oils with higher number of moles of carbon-carbon unsaturated double bond in vegetable oil per kilogram could produce more OH•, which promote the formation of carboxymethyl-PE and carboxyethyl-PE by oxidizing glucose and oil. We elucidated the effects of oils on the formation of glycated phospholipids in terms of OH• and intermediates. This work will contribute to better understanding the formation mechanism of glycated phospholipids with oil.
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Affiliation(s)
- Lipeng Han
- Center for Advanced Analytical Science, School of Chemistry and Chemical Engineering , Guangzhou University , Guangzhou 510006 , China
- Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety , Guangzhou 510640 , China
| | - Qingna Lin
- School of Food Science and Engineering , South China University of Technology , Guangzhou 510640 , China
- Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety , Guangzhou 510640 , China
| | - Guoqin Liu
- School of Food Science and Engineering , South China University of Technology , Guangzhou 510640 , China
- Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety , Guangzhou 510640 , China
| | - Dongxue Han
- Center for Advanced Analytical Science, School of Chemistry and Chemical Engineering , Guangzhou University , Guangzhou 510006 , China
| | - Li Niu
- Center for Advanced Analytical Science, School of Chemistry and Chemical Engineering , Guangzhou University , Guangzhou 510006 , China
| | - Dongxiao Su
- Center for Advanced Analytical Science, School of Chemistry and Chemical Engineering , Guangzhou University , Guangzhou 510006 , China
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20
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Han L, Lin Q, Liu G, Han D, Niu L, Su D. Inhibition Mechanism of Catechin, Resveratrol, Butylated Hydroxylanisole, and Tert-Butylhydroquinone on Carboxymethyl 1,2-Dipalmitoyl-sn-Glycero-3-Phosphatidylethanolamine Formation. J Food Sci 2019; 84:2042-2049. [PMID: 31313292 DOI: 10.1111/1750-3841.14668] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2019] [Revised: 04/23/2019] [Accepted: 04/30/2019] [Indexed: 01/25/2023]
Abstract
It is important to inhibit the food-derived, potentially hazardous chemical glycated lipids by natural products. A model system was established and the products are identified to study the inhibitory mechanism of four types of catechin, resveratrol (RES), and the synthetic antioxidants butylated hydroxylanisole (BHA) and tert-butylhydroquinone (TBHQ) on the formation of carboxymethyl 1,2-dipalmitoyl-sn-glycero-3-phosphatidylethanolamine (CM-DPPE) by determining hydroxyl radical (OH·), Amadori-1,2-dipalmitoyl-sn-glycero-3-phosphatidylethanolamine (Amadori-DPPE) and glyoxal (GO). The results show that the inhibitory rates of catechin and RES on the content of CM-DPPE in the model system are higher than those of BHA and TBHQ. There are at least two inhibitory mechanisms of antioxidants on CM-DPPE. (1) Antioxidants scavenge OH·, which blocks the process of Amadori-DPPE oxidation to form CM-DPPE. (2) Antioxidants trap GO, which blocks the reaction between GO and DPPE to form CM-DPPE. This research will reveal the inhibitory mechanisms of natural antioxidants on glycated lipids from the aspect of scavenging OH· and trapping GO. PRACTICAL APPLICATION: Food manufacturers should pay attention on the production of glycated lipids in food processing. This study will provide the theoretical basis for the use of natural products to inhibit the formation of food-derived glycated lipids. Natural products, such as catechin and resveratrol, can substitute chemical synthesis antioxidants, such as butylated hydroxylanisole and tert-butylhydroquinone, in food processing, which inhibit the formation of glycated lipids.
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Affiliation(s)
- Lipeng Han
- Center for Advanced Analytical Science, School of Chemistry and Chemical Engineering, Guangzhou Univ., Guangzhou, 510006, China.,Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety, Guangzhou, 510640, China
| | - Qingna Lin
- School of Food Science and Engineering, South China Univ. of Technology, Guangzhou, 510640, China
| | - Guoqin Liu
- Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety, Guangzhou, 510640, China.,School of Food Science and Engineering, South China Univ. of Technology, Guangzhou, 510640, China
| | - Dongxue Han
- Center for Advanced Analytical Science, School of Chemistry and Chemical Engineering, Guangzhou Univ., Guangzhou, 510006, China
| | - Li Niu
- Center for Advanced Analytical Science, School of Chemistry and Chemical Engineering, Guangzhou Univ., Guangzhou, 510006, China
| | - Dongxiao Su
- Center for Advanced Analytical Science, School of Chemistry and Chemical Engineering, Guangzhou Univ., Guangzhou, 510006, China
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21
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He X, Chen GY, Zhang Q. Comprehensive Identification of Amadori Compound-Modified Phosphatidylethanolamines in Human Plasma. Chem Res Toxicol 2019; 32:1449-1457. [PMID: 31188577 DOI: 10.1021/acs.chemrestox.9b00158] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Amadori compound modified lipids are the result of nonenzymatic glycation and play an important role in several physiological and pathological processes. However, glycation of phosphatidylethanolamine (PE), the most abundant amine-containing lipid in blood plasma, is underexplored and so far only a few glycated PEs have been reported. Herein, we report comprehensive profiling of Amadori-PE and -LysoPE species in human plasma. Using synthetic standards, we first optimized the enrichment procedure for extracting Amadori-PE/LysoPE from plasma. On the basis of the characteristic neutral losses of 303 Da in positive and 162 Da in negative ionization mode, we then applied neural loss scanning-liquid chromatography tandem mass spectrometry (LC-NLS-MS) to identify potentially glycated PE and LysoPE, which was followed by targeted product ion scanning (LC-PIS-MS) to confidently confirm the fatty acyl substitutions of the modified lipids. A total of 20 Amadori-LysoPE and 62 Amadori-PE species, including diacyl, plasmanyl, and plasmenyl, were identified. Among them, the concentrations of 12 Amarodi-LysoPE and 54 Amadori-PE were also quantified in native human plasma, using stable isotope labeled Amadori lipids as internal standards.
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Affiliation(s)
- Xiaobo He
- Center for Translational Biomedical Research , University of North Carolina at Greensboro , North Carolina Research Campus , Kannapolis , North Carolina 28081 , United States
| | - Guan-Yuan Chen
- Center for Translational Biomedical Research , University of North Carolina at Greensboro , North Carolina Research Campus , Kannapolis , North Carolina 28081 , United States
| | - Qibin Zhang
- Center for Translational Biomedical Research , University of North Carolina at Greensboro , North Carolina Research Campus , Kannapolis , North Carolina 28081 , United States.,Department of Chemistry & Biochemistry , University of North Carolina at Greensboro , Greensboro , North Carolina 27412 , United States
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22
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De Silva GS, Desai K, Darwech M, Naim U, Jin X, Adak S, Harroun N, Sanchez LA, Semenkovich CF, Zayed MA. Circulating serum fatty acid synthase is elevated in patients with diabetes and carotid artery stenosis and is LDL-associated. Atherosclerosis 2019; 287:38-45. [PMID: 31202106 DOI: 10.1016/j.atherosclerosis.2019.05.016] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Revised: 05/04/2019] [Accepted: 05/23/2019] [Indexed: 01/11/2023]
Abstract
BACKGROUND AND AIMS Diabetes is an independent risk factor for carotid artery stenosis (CAS). Fatty acid synthase (FAS), an essential de novo lipogenesis enzyme, has increased activity in the setting of diabetes that leads to altered lipid metabolism. Circulating FAS (cFAS) was recently observed in the blood of patients with hyperinsulinemia and cancer. We thought to evaluate the origin of cFAS and its role in diabetes-associated CAS. METHODS Patients with diabetes and no diabetes, undergoing carotid endarterectomy (CEA) for CAS, were prospectively enrolled for collection of plaque and fasting serum. FPLC was used to purify lipoprotein fractions, and ELISA was used to quantify cFAS content and activity. Immunoprecipitation (IP) was used to evaluate the affinity of cFAS to LDL-ApoB. RESULTS Patients with CAS had higher cFAS activity (p < 0.01), and patients with diabetes had higher cFAS activity than patients with no diabetes (p < 0.05). cFAS activity correlated with serum glucose (p = 0.03, r2 = 0.35), and cFAS content trended with plaque FAS content (p = 0.06, r2 = 0.69). cFAS was predominantly in LDL cholesterol fractions of patients with CAS (p < 0.001), and IP of cFAS demonstrated pulldown of ApoB. Similar to patients with diabetes, db/db mice had highest levels of serum cFAS (p < 0.01), and fasL-/- (tissue-specific liver knockdown of FAS) mice had the lowest levels of cFAS (p < 0.001). CONCLUSIONS Serum cFAS is higher in patients with diabetes and CAS, appears to originate from the liver, and is LDL cholesterol associated. We postulate that LDL may be serving as a carrier for cFAS that contributes to atheroprogression in carotid arteries of patients with diabetes.
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Affiliation(s)
- Gayan S De Silva
- (a)Washington University School of Medicine, Department of Surgery, Section of Vascular Surgery, St. Louis, MO, USA
| | - Kshitij Desai
- (a)Washington University School of Medicine, Department of Surgery, Section of Vascular Surgery, St. Louis, MO, USA
| | - Malik Darwech
- (a)Washington University School of Medicine, Department of Surgery, Section of Vascular Surgery, St. Louis, MO, USA
| | - Uzma Naim
- (a)Washington University School of Medicine, Department of Surgery, Section of Vascular Surgery, St. Louis, MO, USA
| | - Xiaohua Jin
- (a)Washington University School of Medicine, Department of Surgery, Section of Vascular Surgery, St. Louis, MO, USA
| | - Sangeeta Adak
- Washington University School of Medicine, Department of Internal Medicine, Division of Endocrinology, Lipid, and Metabolism, St. Louis, MO, USA
| | - Nikolai Harroun
- (a)Washington University School of Medicine, Department of Surgery, Section of Vascular Surgery, St. Louis, MO, USA
| | - Luis A Sanchez
- (a)Washington University School of Medicine, Department of Surgery, Section of Vascular Surgery, St. Louis, MO, USA
| | - Clay F Semenkovich
- Washington University School of Medicine, Department of Internal Medicine, Division of Endocrinology, Lipid, and Metabolism, St. Louis, MO, USA
| | - Mohamed A Zayed
- (a)Washington University School of Medicine, Department of Surgery, Section of Vascular Surgery, St. Louis, MO, USA; Veterans Affairs St. Louis Health Care System, St. Louis, MO, USA.
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23
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Abstract
Diabetic kidney disease commonly is associated with an increased risk of cardiovascular disease. There are traditional common risk factors for both conditions including hypertension and poor glycemic control. However, it is likely that there are other pathophysiological mechanisms that explain the clinical phenomenon of increased cardiovascular disease in diabetic patients with chronic kidney and vice versa. Current management of both conditions includes aggressive glucose and blood pressure control. The protective role of treating dyslipidemia has been shown for cardiovascular disease, but the results for renal disease are not as clear. The advent of new classes of glucose-lowering agents such as sodium glucose co-transporter2 inhibitors and glucagon-like peptide-1 agonists has resulted in impressive effects on both cardiovascular and renal disease in diabetes. However, how these drugs act independently of glucose lowering to confer both kidney and cardiovascular protection has not been fully elucidated. Nevertheless, these new treatments provide optimism for reducing both microvascular and macrovascular complications in diabetes, which represent the major causes of morbidity and premature mortality in this condition.
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Affiliation(s)
- Muhammad Maqbool
- Department of Diabetes, Central Clinical School, Monash University, Melbourne, Australia
| | - Mark E Cooper
- Department of Diabetes, Central Clinical School, Monash University, Melbourne, Australia
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24
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Han L, Lin Q, Liu G, Han D, Niu L, Su D. Catechin inhibits glycated phosphatidylethanolamine formation by trapping dicarbonyl compounds and forming quinone. Food Funct 2019; 10:2491-2503. [DOI: 10.1039/c9fo00155g] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Catechin inhibits glycated phosphatidylethanolamine formation by trapping dicarbonyl compounds and forming quinone.
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Affiliation(s)
- Lipeng Han
- Center for Advanced Analytical Science
- School of Chemistry and Chemical Engineering
- Guangzhou University
- Guangzhou 510006
- China
| | - Qingna Lin
- School of Food Science and Engineering
- South China University of Technology
- Guangzhou 510640
- China
- Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety
| | - Guoqin Liu
- School of Food Science and Engineering
- South China University of Technology
- Guangzhou 510640
- China
- Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety
| | - Dongxue Han
- Center for Advanced Analytical Science
- School of Chemistry and Chemical Engineering
- Guangzhou University
- Guangzhou 510006
- China
| | - Li Niu
- Center for Advanced Analytical Science
- School of Chemistry and Chemical Engineering
- Guangzhou University
- Guangzhou 510006
- China
| | - Dongxiao Su
- Center for Advanced Analytical Science
- School of Chemistry and Chemical Engineering
- Guangzhou University
- Guangzhou 510006
- China
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25
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He X, Zhang Q. Synthesis, Purification, and Mass Spectrometric Characterization of Stable Isotope-Labeled Amadori-Glycated Phospholipids. ACS OMEGA 2018; 3:15725-15733. [PMID: 30533579 PMCID: PMC6275948 DOI: 10.1021/acsomega.8b01893] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/03/2018] [Accepted: 11/06/2018] [Indexed: 06/09/2023]
Abstract
Nonenzymatic glycation of lipids plays an important role in several physiological and pathological processes, such as normal aging and complications of diabetes mellitus. To develop liquid chromatography coupled with mass spectrometric (LC-MS) methods for accurate analysis of Amadori compound-glycated lipids from biological samples, it is essential to obtain isotope-labeled Amadori-lipid standards. Herein, we report optimized methods for the preparation of six stable isotope-labeled Amadori-glycated lipid standards covering four types of lipids, including [13C6]Amadori-phosphatidyl ethanolamine (PE), -phosphatidyl serine (PS), -LysoPE, and -LysoPS. Optimal conditions for the synthesis and purification of these four types of Amadori-glycated lipids were detailed in this study. LC-MS and LC-UV analyses showed that destination products were highly purified (>95%). Accurate mass and MS/MS fragmentation in both positive- and negative-ion modes further validated the identification of these six synthetic [13C6]Amadori-glycated lipid standards. Successful preparation of these highly purified isotope-labeled standards makes it possible to develop targeted LC-MS/MS methods for accurate analysis of Amadori-glycated phospholipids from biological samples.
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Affiliation(s)
- Xiaobo He
- Center for Translational
Biomedical Research, University of North
Carolina at Greensboro, North Carolina
Research Campus, Kannapolis, North Carolina 28081, United States
| | - Qibin Zhang
- Center for Translational
Biomedical Research, University of North
Carolina at Greensboro, North Carolina
Research Campus, Kannapolis, North Carolina 28081, United States
- Department of Chemistry & Biochemistry, University of North Carolina at Greensboro, Greensboro, North Carolina 27412, United States
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26
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Klaus A, Rau R, Glomb MA. Modification and Cross-Linking of Proteins by Glycolaldehyde and Glyoxal: A Model System. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2018; 66:10835-10843. [PMID: 30296075 DOI: 10.1021/acs.jafc.8b04023] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
Highly reactive intermediates of the Maillard reaction, such as glycolaldehyde and glyoxal, are precursors in the modification and cross-linking of proteins. Therefore, we investigated ribonuclease A modified by glycolaldehyde and glyoxal, separately. For the first time, various protein species derived by these aldehydes were successfully separated by ion-exchange chromatography and gel permeation chromatography. Highly cross-linked ribonuclease A was obtained in glycolaldehyde incubations. In contrast, glyoxal predominantly led to modified monomeric protein species. These results were verified by sodium dodecyl sulfate polyacrylamide gel electrophoresis and isoelectric focusing. Quantitation of mono- and bivalent protein modifications of the isolated protein species led to a positive correlation between the degree of protein modification and the change of the isoelectric point and molecular weight, respectively. Glycolaldehyde is easily oxidized to glyoxal. However, significantly lower levels of bivalent glyoxal modifications were detected in glycolaldehyde versus glyoxal incubations (glyoxal-lysine dimer, 1.58 ± 0.02 versus 2.86 ± 0.04 mmol/mol of phenylalanine; glyoxal-lysine amide, 2.7 ± 0.1 versus 5.6 ± 0.1 mmol/mol of phenylalanine). In addition, a novel glycolaldehyde-specific lysine-lysine cross-link was identified and putatively assigned as 1-(5-amino-5-carboxypentyl)-4-(5-amino-5-carboxypentyl-amino)pyridinium salt.
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Affiliation(s)
- Alexander Klaus
- Institute of Chemistry, Food Chemistry , Martin-Luther-University Halle-Wittenberg , Kurt-Mothes-Straße 2 , 06120 Halle/Saale , Germany
| | - Robert Rau
- Institute of Chemistry, Food Chemistry , Martin-Luther-University Halle-Wittenberg , Kurt-Mothes-Straße 2 , 06120 Halle/Saale , Germany
| | - Marcus A Glomb
- Institute of Chemistry, Food Chemistry , Martin-Luther-University Halle-Wittenberg , Kurt-Mothes-Straße 2 , 06120 Halle/Saale , Germany
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27
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Intestinal Saturated Long-Chain Fatty Acid, Glucose and Fructose Transporters and Their Inhibition by Natural Plant Extracts in Caco-2 Cells. Molecules 2018; 23:molecules23102544. [PMID: 30301205 PMCID: PMC6222386 DOI: 10.3390/molecules23102544] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2018] [Revised: 09/29/2018] [Accepted: 10/04/2018] [Indexed: 02/07/2023] Open
Abstract
The intestinal absorption of fatty acids, glucose and fructose is part of the basic requirements for the provision of energy in the body. High access of saturated long-chain fatty acids (LCFA), glucose and fructose can facilitate the development of metabolic diseases, particularly the metabolic syndrome and type-2 diabetes mellitus (T2DM). Research has been done to find substances which decelerate or inhibit intestinal resorption of these specific food components. Promising targets are the inhibition of intestinal long-chain fatty acid (FATP2, FATP4), glucose (SGLT1, GLUT2) and fructose (GLUT2, GLUT5) transporters by plant extracts and by pure substances. The largest part of active components in plant extracts belongs to the group of polyphenols. This review summarizes the knowledge about binding sites of named transporters and lists the plant extracts which were tested in Caco-2 cells regarding uptake inhibition.
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28
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Borire AA, Issar T, Kwai NC, Visser LH, Simon NG, Poynten AM, Kiernan MC, Krishnan AV. Correlation between markers of peripheral nerve function and structure in type 1 diabetes. Diabetes Metab Res Rev 2018; 34:e3028. [PMID: 29858541 DOI: 10.1002/dmrr.3028] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2018] [Revised: 05/20/2018] [Accepted: 05/28/2018] [Indexed: 12/19/2022]
Abstract
BACKGROUND Clinical and experimental studies in patients with type 1 and type 2 diabetes have demonstrated changes in ion channel function and nerve structure. In this study, we investigated the relationship between axonal dysfunction and morphological change in diabetic polyneuropathy by using neuromuscular ultrasound and nerve excitability techniques. We also explored possible differences in this relationship between type 1 and type 2 diabetes. METHODS Nerve ultrasound and corresponding motor excitability studies were undertaken in 110 diabetes patients (50 type 1; 60 type 2) and 60 age-matched controls (30 for each group). Neuropathy severity was assessed by using total neuropathy score. Median and tibial nerve cross-sectional areas were measured at nonentrapment sites by using high-resolution linear probe. RESULTS Median and tibial nerve cross-sectional areas were significantly higher in diabetes patients compared with controls: type 1 (median = 7.6 ± 0.2 mm2 vs 6.3 ± 0.1 mm2 ; tibial = 14.5 ± 0.7 mm2 vs 10.8 ± 0.3 mm2 , P < .05) and type 2 (median = 9.1 ± 0.3 mm2 vs 7.2 ± 0.1 mm2 ; tibial = 18.5 ± 1.0 mm2 vs 12.8 ± 0.5 mm2 , P < .05). In the type 1 cohort, significant correlations were found between nerve cross-sectional area and excitability parameters including resting current-threshold slope (median: r = 0.523, P < .0001; tibial: r = -0.571, P = .004) and depolarizing threshold electrotonus at 90 to 100 ms (median: 0.424, P < .01; tibial: r = 0.435, P = .030). In contrast, there was no relationship between excitability values and nerve cross-sectional area in the type 2 cohort. CONCLUSIONS This study has identified correlation between markers of axonal membrane function and structural abnormalities in peripheral nerves of type 1 diabetes patients. The differential relationship in nerve function and structure between type 1 and type 2 diabetes provides clinical evidence that different pathophysiological mechanisms underlie the development of neuropathy in these patient groups.
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Affiliation(s)
- Adeniyi A Borire
- University of New South Wales, Prince of Wales Clinical School, Sydney, New South Wales, Australia
| | - Tushar Issar
- University of New South Wales, Prince of Wales Clinical School, Sydney, New South Wales, Australia
| | - Natalie C Kwai
- University of New South Wales, School of Medical Sciences, Sydney, New South Wales, Australia
| | - Leo H Visser
- St Elisabeth Ziekenhuis, Tilburg, The Netherlands
| | - Neil G Simon
- University of New South Wales, St Vincent's Clinical School, Sydney, New South Wales, Australia
- University of Sydney, Brain and Mind Centre, Sydney, New South Wales, Australia
| | - Ann M Poynten
- Prince of Wales Hospital, Department of Endocrinology, Sydney, New South Wales, Australia
| | - Matthew C Kiernan
- University of Sydney, Brain and Mind Centre, Sydney, New South Wales, Australia
| | - Arun V Krishnan
- University of New South Wales, Prince of Wales Clinical School, Sydney, New South Wales, Australia
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29
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Immunochemical studies on native and glycated LDL – An approach to uncover the structural perturbations. Int J Biol Macromol 2018; 115:287-299. [DOI: 10.1016/j.ijbiomac.2018.04.016] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2018] [Revised: 03/20/2018] [Accepted: 04/04/2018] [Indexed: 01/27/2023]
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30
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Critical Appraisal of Advanced Glycation End Products (AGEs) and Circulating Soluble Receptors for Advanced Glycation End Products (sRAGE) as a Predictive Biomarkers for Cardiovascular Disease in Hemodialysis Patients. Med Sci (Basel) 2018; 6:medsci6020038. [PMID: 29789493 PMCID: PMC6024807 DOI: 10.3390/medsci6020038] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2018] [Revised: 05/05/2018] [Accepted: 05/15/2018] [Indexed: 12/26/2022] Open
Abstract
The interaction of advanced glycation end products (AGE) and their receptors promote vascular complications of diabetes in hemodialysis (HD) patients. The soluble form of the receptor for the advanced glycation end-products (sRAGE) has been studied as a vascular biomarker in various diseases with controversial results. Our aim was to evaluate the association of the serum levels of the AGEs and their receptor sRAGE with cardiovascular disease (CVD) and the cardiovascular risk factors among HD patients. There were 130 HD patients and 80 age and gender matched control subjects were involved; 31.5% of the HD group were diabetic, which was an underlying cause of renal impairment; 36.1% had CVD, which was comprising 44.7% of diabetics and 55.3% of non-diabetic patients. The AGEs and sRAGE were assessed by enzyme linked immunosorbent assay (ELISA). In addition, the lipid profile, glycemic indices, pre-dialysis renal function tests, and hemoglobin % (Hb) were evaluated. The results show that the circulating AGEs and sRAGE levels were significantly higher in the HD patients. Those with underlying diabetes displayed higher sRAGE levels, which were positively correlated with hyperglycemia, HbA1C, and total cholesterol (TC). The HD patients with an increased serum sRAGE exhibited more cardiovascular risk factors (hypercholesterolemia and anemia) with a high prevalence of CVD. Using a linear regression analysis, we found a significant association of sRAGE with CVD and TC among HD patients, regardless of whether associating diabetes was an underlying cause of renal impairment. Overall, the HD patients displayed significantly higher serum AGEs with a concomitant increase in the circulating sRAGE levels, mainly in the diabetic HD, which were significantly associated with the CVD (independent predictors) and CV risk factors (hypercholesterolemia), mainly sRAGEs, regardless of the underlying diabetes mellitus. This highlights the prognostic role of AGEs and sRAGE in HD patients regardless of underlying cause in order to predict the risk for CVD.
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31
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Zayed MA, Hsu FF, Patterson BW, Yan Y, Naim U, Darwesh M, De Silva G, Yang C, Semenkovich CF. Diabetes adversely affects phospholipid profiles in human carotid artery endarterectomy plaques. J Lipid Res 2018; 59:730-738. [PMID: 29478028 PMCID: PMC5880490 DOI: 10.1194/jlr.m081026] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2017] [Revised: 02/21/2018] [Indexed: 12/22/2022] Open
Abstract
Patients with diabetes are at higher risk of developing carotid artery stenosis and resultant stroke. Arachidonoyl phospholipids affect plaque inflammation and vulnerability, but whether diabetic patients have unique carotid artery phospholipidomic profiles is unknown. We performed a comprehensive paired analysis of phospholipids in extracranial carotid endarterectomy (CEA) plaques of matched diabetic and nondiabetic patients and analyzed mass spectrometry-derived profiles of three phospholipids, plasmenyl-phosphatidylethanolamine (pPE), phosphatidylserine (PS), and phosphatidylinositol (PI), in maximally (MAX) and minimally (MIN) diseased CEA segments. We also measured levels of arachidonic acid (AA), produced by pPE hydrolysis, and choline-ethanolamine phosphotransferase 1 (CEPT1), responsible for most pPE de novo biosynthesis. In paired analysis, MIN CEA segments had higher levels than MAX segments of pPE (P < 0.001), PS (P < 0.001), and PI (P < 0.03). MIN diabetic plaques contained higher levels than MAX diabetic plaques of arachidonoyl pPE38:4 and pPE38:5 and CEPT1 was upregulated in diabetic versus nondiabetic plaques. AA levels were relatively greater in MIN versus MAX segments of all CEA segments, and were higher in diabetic than nondiabetic plaques. Our findings suggest that arachidonoyl phospholipids are more likely to be abundant in the extracranial carotid artery plaque of diabetic rather than nondiabetic patients.
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Affiliation(s)
- Mohamed A Zayed
- Section of Vascular Surgery, Department of Surgery, Center for Human Nutrition Washington University School of Medicine, St. Louis, MO; Department of Surgery, Veterans Affairs St. Louis Health Care System, St. Louis, MO.
| | - Fong-Fu Hsu
- Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University, St. Louis, MO
| | - Bruce W Patterson
- Department of Medicine, and Division of Public Health Sciences, Washington University School of Medicine, St. Louis, MO
| | - Yan Yan
- Department of Surgery, Washington University School of Medicine, St. Louis, MO
| | - Uzma Naim
- Section of Vascular Surgery, Department of Surgery, Center for Human Nutrition Washington University School of Medicine, St. Louis, MO
| | - Malik Darwesh
- Section of Vascular Surgery, Department of Surgery, Center for Human Nutrition Washington University School of Medicine, St. Louis, MO
| | - Gayan De Silva
- Section of Vascular Surgery, Department of Surgery, Center for Human Nutrition Washington University School of Medicine, St. Louis, MO
| | - Chao Yang
- Section of Vascular Surgery, Department of Surgery, Center for Human Nutrition Washington University School of Medicine, St. Louis, MO
| | - Clay F Semenkovich
- Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University, St. Louis, MO
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32
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Zhu Y, Snooks H, Sang S. Complexity of Advanced Glycation End Products in Foods: Where Are We Now? JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2018; 66:1325-1329. [PMID: 29378411 DOI: 10.1021/acs.jafc.7b05955] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
Recent clinical trials indicate that consumption of dietary advanced glycation end products (AGEs) may promote the development of major chronic diseases. However, the outcomes of human studies have proven inconclusive as a result of estimates of the total AGE intake being taken with a single AGE in most of the studies. In this perspective, we summarized the major types of AGEs derived from proteins, nucleic acids, and phospholipids during food processing and suggested a panel of AGEs as markers to better measure the intake of total dietary AGEs in human studies.
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Affiliation(s)
- Yingdong Zhu
- Laboratory for Functional Foods and Human Health, Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University , North Carolina Research Campus, 500 Laureate Way, Kannapolis, North Carolina 28081, United States
| | - Hunter Snooks
- Laboratory for Functional Foods and Human Health, Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University , North Carolina Research Campus, 500 Laureate Way, Kannapolis, North Carolina 28081, United States
| | - Shengmin Sang
- Laboratory for Functional Foods and Human Health, Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University , North Carolina Research Campus, 500 Laureate Way, Kannapolis, North Carolina 28081, United States
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33
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Li KJ, Borresen EC, Jenkins-Puccetti N, Luckasen G, Ryan EP. Navy Bean and Rice Bran Intake Alters the Plasma Metabolome of Children at Risk for Cardiovascular Disease. Front Nutr 2018; 4:71. [PMID: 29404331 PMCID: PMC5786740 DOI: 10.3389/fnut.2017.00071] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Accepted: 12/20/2017] [Indexed: 12/31/2022] Open
Abstract
Abnormal cholesterol in childhood predicts cardiovascular disease (CVD) risk in adulthood. Navy beans and rice bran have demonstrated efficacy in regulating blood lipids in adults and children; however, their effects on modulating the child plasma metabolome has not been investigated and warrants investigation. A pilot, randomized-controlled, clinical trial was conducted in 38 children (10 ± 0.8 years old) with abnormal cholesterol. Participants consumed a snack for 4 weeks containing either: no navy bean or rice bran (control); 17.5 g/day cooked navy bean powder; 15 g/day heat-stabilized rice bran; or 9 g/day navy beans and 8 g/day rice bran. Plasma metabolites were extracted using 80% methanol for global, non-targeted metabolic profiling via ultra-high performance liquid-chromatography tandem mass spectrometry. Differences in plasma metabolite levels after 4 weeks of dietary intervention compared to control and baseline were analyzed using analysis of variance and Welch's t-tests (p ≤ 0.05). Navy bean and/or rice bran consumption influenced 71 plasma compounds compared to control (p ≤ 0.05), with lipids representing 46% of the total plasma metabolome. Significant changes were determined for 18 plasma lipids in the navy bean group and 10 plasma lipids for the rice bran group compared to control, and 48 lipids in the navy bean group and 40 in the rice bran group compared to baseline. These results support the hypothesis that consumption of these foods impact blood lipid metabolism with implications for reducing CVD risk in children. Complementary and distinct lipid pathways were affected by the diet groups, including acylcarnitines and lysolipids (navy bean), sphingolipids (rice bran), and phospholipids (navy bean + rice bran). Navy bean consumption decreased free fatty acids associated with metabolic diseases (palmitate and arachidonate) and increased the relative abundance of endogenous anti-inflammatory lipids (endocannabinoids, N-linoleoylglycine, 12,13-diHOME). Several diet-derived amino acids, phytochemicals, and cofactors/vitamins with cardioprotective properties were increased compared to control and/or baseline, including 6-oxopiperidine-2-carboxylate (1.87-fold), N-methylpipecolate (1.89-fold), trigonelline (4.44- to 7.75-fold), S-methylcysteine (2.12-fold) (navy bean), salicylate (2.74-fold), and pyridoxal (3.35- to 3.96-fold) (rice bran). Findings from this pilot study support the need for investigating the effects of these foods for longer durations to reduce CVD risk. TRIAL REGISTRATION clinicaltrials.gov (identifier NCT01911390).
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Affiliation(s)
- Katherine J. Li
- Nutrition and Toxicology Laboratory, Department of Environmental and Radiological Health Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States
| | - Erica C. Borresen
- Nutrition and Toxicology Laboratory, Department of Environmental and Radiological Health Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States
| | - NaNet Jenkins-Puccetti
- Medical Center of the Rockies, University of Colorado Health Research – Northern Region, Loveland, CO, United States
| | - Gary Luckasen
- Medical Center of the Rockies, University of Colorado Health Research – Northern Region, Loveland, CO, United States
| | - Elizabeth P. Ryan
- Nutrition and Toxicology Laboratory, Department of Environmental and Radiological Health Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States
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34
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Lin Q, Han L, Liu G, Cheng W, Wang L. A preliminary study on the formation pathways of glycated phosphatidylethanolamine of food rich in phospholipid during the heat-processing. RSC Adv 2018; 8:11280-11288. [PMID: 35542782 PMCID: PMC9078963 DOI: 10.1039/c8ra01072b] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2018] [Accepted: 03/08/2018] [Indexed: 11/21/2022] Open
Abstract
The formation of food-derived glycated phosphatidylethanolamine (PE) in thermal process was investigated by designing a 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE)-glucose model system heated from 40 to 100 °C for 8 h.
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Affiliation(s)
- Qingna Lin
- School of Food Science and Engineering
- South China University of Technology
- Guangzhou 510640
- China
| | - Lipeng Han
- School of Chemistry and Chemical Engineering
- Guangzhou University
- Guangzhou 510006
- China
- Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety
| | - Guoqin Liu
- School of Food Science and Engineering
- South China University of Technology
- Guangzhou 510640
- China
- Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety
| | - Weiwei Cheng
- School of Food Science and Engineering
- South China University of Technology
- Guangzhou 510640
- China
| | - Liqing Wang
- Guangdong Testing Institute of Product Quality Supervision
- Guangzhou 510670
- China
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35
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Lüscher B, Bütepage M, Eckei L, Krieg S, Verheugd P, Shilton BH. ADP-Ribosylation, a Multifaceted Posttranslational Modification Involved in the Control of Cell Physiology in Health and Disease. Chem Rev 2017; 118:1092-1136. [PMID: 29172462 DOI: 10.1021/acs.chemrev.7b00122] [Citation(s) in RCA: 177] [Impact Index Per Article: 22.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Posttranslational modifications (PTMs) regulate protein functions and interactions. ADP-ribosylation is a PTM, in which ADP-ribosyltransferases use nicotinamide adenine dinucleotide (NAD+) to modify target proteins with ADP-ribose. This modification can occur as mono- or poly-ADP-ribosylation. The latter involves the synthesis of long ADP-ribose chains that have specific properties due to the nature of the polymer. ADP-Ribosylation is reversed by hydrolases that cleave the glycosidic bonds either between ADP-ribose units or between the protein proximal ADP-ribose and a given amino acid side chain. Here we discuss the properties of the different enzymes associated with ADP-ribosylation and the consequences of this PTM on substrates. Furthermore, the different domains that interpret either mono- or poly-ADP-ribosylation and the implications for cellular processes are described.
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Affiliation(s)
- Bernhard Lüscher
- Institute of Biochemistry and Molecular Biology, Medical School, RWTH Aachen University , 52057 Aachen, Germany
| | - Mareike Bütepage
- Institute of Biochemistry and Molecular Biology, Medical School, RWTH Aachen University , 52057 Aachen, Germany
| | - Laura Eckei
- Institute of Biochemistry and Molecular Biology, Medical School, RWTH Aachen University , 52057 Aachen, Germany
| | - Sarah Krieg
- Institute of Biochemistry and Molecular Biology, Medical School, RWTH Aachen University , 52057 Aachen, Germany
| | - Patricia Verheugd
- Institute of Biochemistry and Molecular Biology, Medical School, RWTH Aachen University , 52057 Aachen, Germany
| | - Brian H Shilton
- Institute of Biochemistry and Molecular Biology, Medical School, RWTH Aachen University , 52057 Aachen, Germany.,Department of Biochemistry, Schulich School of Medicine & Dentistry, The University of Western Ontario , Medical Sciences Building Room 332, London, Ontario Canada N6A 5C1
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36
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Raghav A, Ahmad J, Alam K, Khan AU. New insights into non-enzymatic glycation of human serum albumin biopolymer: A study to unveil its impaired structure and function. Int J Biol Macromol 2017; 101:84-99. [DOI: 10.1016/j.ijbiomac.2017.03.086] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2017] [Revised: 03/13/2017] [Accepted: 03/15/2017] [Indexed: 12/31/2022]
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37
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Zarei M, Fakher S, Tabei SMB, Javanbakht MH, Derakhshanian H, Farahbakhsh-Farsi P, Sadeghi MR, Mostafavi E, Djalali M. Effects of vitamin A, C and E, or omega-3 fatty acid supplementation on the level of paraoxonase and arylesterase activity in streptozotocin-induced diabetic rats: an investigation of activities in plasma, and heart and liver homogenates. Singapore Med J 2017; 57:153-6. [PMID: 26996784 DOI: 10.11622/smedj.2015102] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
INTRODUCTION This study was designed and conducted to evaluate the effects of vitamin A, C and E supplementation, and omega-3 fatty acid supplementation on the activity of paraoxonase and arylesterase in an experimental model of diabetes mellitus. METHODS A total of 64 male Sprague Dawley® rats, each weighing 250 g, were randomly distributed into four groups: (a) normal control; (b) diabetic control; (c) diabetic with vitamin A, C and E supplementation; and (d) diabetic with omega-3 fatty acid supplementation. The animals were anaesthetised after four weeks of intervention, and paraoxonase and arylesterase activity in blood plasma, and liver and heart homogenates were measured. RESULTS Arylesterase activity in the heart and liver homogenates was significantly lower in the diabetic control group than in the normal control group (p < 0.01). Vitamin A, C and E supplementation, and omega-3 fatty acid supplementation significantly increased liver arylesterase activity (p < 0.05). No significant change was observed in paraoxonase activity and other investigated factors. CONCLUSION Vitamin A, C and E, or omega-3 fatty acid supplementation were found to increase liver arylesterase activity in streptozotocin-induced diabetic rats. These supplements may be potential agents for the treatment of diabetes mellitus complications.
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Affiliation(s)
- Mahnaz Zarei
- Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Shima Fakher
- Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Mohammad Hassan Javanbakht
- Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Hoda Derakhshanian
- Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Payam Farahbakhsh-Farsi
- Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Sadeghi
- Department of Reproductive Endocrinology and Embryology, Avesina Research Institute, Tehran, Iran
| | - Ebrahim Mostafavi
- Department of Pathology, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahmoud Djalali
- Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
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Ahmed A, Shamsi A, Bano B. Characterizing harmful advanced glycation end-products (AGEs) and ribosylated aggregates of yellow mustard seed phytocystatin: Effects of different monosaccharides. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2017; 171:183-192. [PMID: 27526342 DOI: 10.1016/j.saa.2016.08.004] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/17/2016] [Revised: 07/20/2016] [Accepted: 08/04/2016] [Indexed: 06/06/2023]
Abstract
Advanced glycation end products (AGEs) are at the core of variety of diseases ranging from diabetes to renal failure and hence gaining wide consideration. This study was aimed at characterizing the AGEs of phytocystatin isolated from mustard seeds (YMP) when incubated with different monosaccharides (glucose, ribose and mannose) using fluorescence, ultraviolet, circular dichroism (CD) spectroscopy and microscopy. Ribose was found to be the most potent glycating agent as evident by AGEs specific fluorescence and absorbance. YMP exists as a molten globule like structure on day 24 as depicted by high ANS fluorescence and altered intrinsic fluorescence. Glycated YMP as AGEs and ribose induced aggregates were observed at day 28 and 32 respectively. In our study we have also examined the anti-aggregative potential of polyphenol, resveratrol. Our results suggested the anti-aggregative behavior of resveratrol as it prevented the in vitro aggregation of YMP, although further studies are required to decode the mechanism by which resveratrol prevents the aggregation.
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Affiliation(s)
- Azaj Ahmed
- Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, India
| | - Anas Shamsi
- Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, India
| | - Bilqees Bano
- Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, India.
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Zemski Berry KA, Barkley RM, Berry JJ, Hankin JA, Hoyes E, Brown JM, Murphy RC. Tandem Mass Spectrometry in Combination with Product Ion Mobility for the Identification of Phospholipids. Anal Chem 2017; 89:916-921. [PMID: 27958700 PMCID: PMC5250582 DOI: 10.1021/acs.analchem.6b04047] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Concerted tandem and traveling wave ion mobility mass spectrometry (CTS analysis) is a unique method that results in a four-dimensional data set including nominal precursor ion mass, product ion mobility, accurate mass of product ion, and ion abundance. This nontargeted lipidomics CTS approach was applied in both positive- and negative-ion mode to phospholipids present in human serum, and the data set was used to evaluate the value of product ion mobility in identifying lipids in a complex mixture. It was determined that the combination of diagnostic product ions and unique collisional cross-section values of product ions is a powerful tool in the structural identification of lipids in a complex biological sample.
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Affiliation(s)
- Karin A. Zemski Berry
- Department of Pharmacology, University of Colorado Denver, Mail Stop 8303, 12801 E. 17 Ave, Aurora, CO 80045
| | - Robert M. Barkley
- Department of Pharmacology, University of Colorado Denver, Mail Stop 8303, 12801 E. 17 Ave, Aurora, CO 80045
| | - Joseph J. Berry
- National Renewable Energy Laboratory, 15013 Denver W Pkwy, Golden, CO 80401
| | - Joseph A. Hankin
- Department of Pharmacology, University of Colorado Denver, Mail Stop 8303, 12801 E. 17 Ave, Aurora, CO 80045
| | - Emmy Hoyes
- Waters Corporation, Altrincham Road, Wilmslow, SK9 4AX, United Kingdom
| | - Jeffery M. Brown
- Waters Corporation, Altrincham Road, Wilmslow, SK9 4AX, United Kingdom
| | - Robert C. Murphy
- Department of Pharmacology, University of Colorado Denver, Mail Stop 8303, 12801 E. 17 Ave, Aurora, CO 80045
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Henning C, Glomb MA. Pathways of the Maillard reaction under physiological conditions. Glycoconj J 2016; 33:499-512. [DOI: 10.1007/s10719-016-9694-y] [Citation(s) in RCA: 81] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2016] [Revised: 05/27/2016] [Accepted: 05/27/2016] [Indexed: 10/21/2022]
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Lankin VZ, Konovalova GG, Tikhaze AK, Shumaev KB, Belova Kumskova EM, Grechnikova MA, Viigimaa M. Aldehyde inhibition of antioxidant enzymes in the blood of diabetic patients. J Diabetes 2016; 8:398-404. [PMID: 25990785 DOI: 10.1111/1753-0407.12309] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2014] [Revised: 03/30/2015] [Accepted: 05/03/2015] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND The aim of the present study was to examine the effect of aldehyde modification on antioxidant enzyme activity in diabetic patients. METHODS The activity of commercially available antioxidant enzymes (catalase, glutathione peroxidase [GPx], and Cu,Zn-superoxide dismutase [SOD]) was determined in vitro prior to and after aldehyde modification. The activity of erythrocyte Cu,Zn-SOD was assayed in blood drawn from healthy donors, diabetic patients with decompensated carbohydrate metabolism, and diabetic patients after glucose-lowering therapy. RESULTS In vitro aldehyde modification had no effect on catalase activity, but diminished GPx and Cu,Zn-SOD activity. In diabetic patients with decompensated carbohydrate metabolism, glucose-lowering therapy significantly increased Cu,Zn-SOD activity, the effect being especially pronounced after administration of metformin. CONCLUSIONS It is likely that metformin antagonizes the aldehyde-induced inhibition of erythrocyte Cu,Zn-SOD in diabetic patients more effectively than sulfonylurea drugs.
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Marungruang N, Fåk F, Tareke E. Heat-treated high-fat diet modifies gut microbiota and metabolic markers in apoe-/- mice. Nutr Metab (Lond) 2016; 13:22. [PMID: 26973703 PMCID: PMC4788960 DOI: 10.1186/s12986-016-0083-0] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2016] [Accepted: 03/06/2016] [Indexed: 02/08/2023] Open
Abstract
Background High-fat diet has been known to have adverse effects on metabolic markers, as well as the gut microbiota. However, the effect of heat processing of high-fat diet, which leads to formations of advanced glycation end products (AGEs) has not been clearly distinguished from the effect of unheated fat. This study compared the effect of high-fat diet with heat-treated high-fat diet on adiposity, atherosclerosis and gut microbiota composition in the caecum of apoe−/− mice. Method Male apoe−/− mice were fed either low-fat (LF) control diet, high-fat (40 E% saturated fat, HF) control diet, or heat-treated high-fat (200 °C for 10 min, HT) diet, for 8 weeks. The plasma samples were used in the analysis of Nε-carboxy-methyl-lysine (CML) and Nε-carboxy-ethyl-lysine (CEL). The heart samples were analysed for atherosclerotic plaques, and the DNA from caecum was extracted and analysed for microbiota composition using 16S rRNA gene sequencing on a Miseq instrument. Additionally, the functions of microbial communities were also predicted based on the bacterial 16S rRNA gene sequence using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). Results Here we found that HT modifies gut microbiota composition and host adiposity. Prediction of bacterial gene functions based on 16S rRNA gene sequence revealed that HF increased bacterial genera enriched in lipid metabolism genes, while HT did not. Plasma CML and CEL increased 1.7 and 2.5 times, respectively, in mice fed HT as compared to mice fed HF. Despite lower adiposity, mice fed HT maintained atherosclerosis and displayed enlarged spleens. Conclusions The results suggested that heat processing of high-fat diet modifies the substrates reaching the lower gut of apoe−/− mice, resulting in different effects on gut microbiota composition. AGEs seem to maintain the effect on atherosclerosis, despite lower adiposity, and causing enlarged spleens, which possibly reflect elevated levels of inflammation in the body. Electronic supplementary material The online version of this article (doi:10.1186/s12986-016-0083-0) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Nittaya Marungruang
- Food for Health Science Centre, Lund University, Medicon Village, Scheelevägen 2, SE-223 81 Lund, Sweden
| | - Frida Fåk
- Food for Health Science Centre, Lund University, Medicon Village, Scheelevägen 2, SE-223 81 Lund, Sweden
| | - Eden Tareke
- Food for Health Science Centre, Lund University, Medicon Village, Scheelevägen 2, SE-223 81 Lund, Sweden
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Jayakody LN, Ferdouse J, Hayashi N, Kitagaki H. Identification and detoxification of glycolaldehyde, an unattended bioethanol fermentation inhibitor. Crit Rev Biotechnol 2016; 37:177-189. [PMID: 26953525 DOI: 10.3109/07388551.2015.1128877] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Although there have been approximately 60 chemical compounds identified as potent fermentation inhibitors in lignocellulose hydrolysate, our research group recently discovered glycolaldehyde as a key fermentation inhibitor during second generation biofuel production. Accordingly, we have developed a yeast S. cerevisiae strain exhibiting tolerance to glycolaldehyde. During this glycolaldehyde study, we established novel approaches for rational engineering of inhibitor-tolerant S. cerevisiae strains, including engineering redox cofactors and engineering the SUMOylation pathway. These new technical dimensions provide a novel platform for engineering S. cerevisiae strains to overcome one of the key barriers for industrialization of lignocellulosic ethanol production. As such, this review discusses novel biochemical insight of glycolaldehyde in the context of the biofuel industry.
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Affiliation(s)
- Lahiru N Jayakody
- a Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign , Urbana , IL , USA.,b Department of Biochemistry and Applied Biosciences United Graduate School of Agricultural Sciences , Kagoshima University , Kagoshima , Japan , and
| | - Jannatul Ferdouse
- c Department of Environmental Sciences Faculty of Agriculture , Saga University , Saga , Japan
| | - Nobuyuki Hayashi
- c Department of Environmental Sciences Faculty of Agriculture , Saga University , Saga , Japan
| | - Hiroshi Kitagaki
- b Department of Biochemistry and Applied Biosciences United Graduate School of Agricultural Sciences , Kagoshima University , Kagoshima , Japan , and.,c Department of Environmental Sciences Faculty of Agriculture , Saga University , Saga , Japan
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Cahn A, Cernea S, Raz I. Outcome studies and safety as guide for decision making in treating patients with type 2 diabetes. Rev Endocr Metab Disord 2016; 17:117-27. [PMID: 27106831 DOI: 10.1007/s11154-016-9351-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Cardiovascular disease is the leading cause of mortality in patients with diabetes. Over the past 20 years multiple CV outcome studies have been conducted assessing the cardiovascular benefits of tight glycemic control or of particular glucose lowering agents. Improved glycemic control per-se failed to significantly reduce the risk of adverse cardiovascular outcomes in the short term, and it is only after >15 years that a reduction in adverse CV outcomes with tight glycemic control was perceived. Moreover tight glycemic control and increased attendant hypoglycemia led to increased mortality observed in the ACCORD trial. These data highlighted the importance of setting individualized glycemic targets and assessing the CV safety of the individual glucose lowering agents. Three DPP-4 inhibitors have presented CV outcome data to date demonstrating overall CV safety yet the question of increased hospitalization for heart failure with saxagliptin remains unexplained. Lixisenatide was the first GLP-1 receptor agonist to publish CV outcome data which demonstrated overall safety. The SGLT-2 inhibitor empagliflozin demonstrated CV superiority and a reduction in all-cause mortality and hospitalization for heart failure vs. placebo via mechanisms which remain to be fully elucidated. The outcome studies, though large and costly, have had a considerable effect on diabetes guidelines, these now emphasizing the importance of individualization of care. The outcome studies will presumably influence the new guidelines and dictate better tailoring of the drug regimen to the individual patient, matching patient comorbidities to the accumulating data regarding the safety and efficacy of each drug and class.
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Affiliation(s)
- Avivit Cahn
- Diabetes Unit, Department of Internal Medicine, Hadassah Hebrew University Hospital, PO Box 12000, 91120, Jerusalem, Israel
- Endocrinology and Metabolism Unit, Department of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel
| | - Simona Cernea
- Department M3/Internal Medicine IV, University of Medicine and Pharmacy, Târgu Mureş, Romania
- Diabetes, Nutrition and Metabolic Diseases Outpatient Unit, Emergency County Clinical Hospital, Târgu Mureş, Romania
| | - Itamar Raz
- Diabetes Unit, Department of Internal Medicine, Hadassah Hebrew University Hospital, PO Box 12000, 91120, Jerusalem, Israel.
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Wang CC, Wang YC, Wang GJ, Shen MY, Chang YL, Liou SY, Chen HC, Chang CT. Skin Autofluorescence Is Associated with Endothelial Dysfunction in Uremic Subjects on Hemodialysis. PLoS One 2016; 11:e0147771. [PMID: 26809145 PMCID: PMC4726548 DOI: 10.1371/journal.pone.0147771] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2015] [Accepted: 01/07/2016] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Elevated levels of advanced glycation end products (AGEs) within tissues may contribute to endothelial dysfunction, an early indicator of atherosclerosis. We aimed to investigate whether levels of skin AGEs could be a useful marker to predict endothelial dysfunction in uremic subjects on hemodialysis. METHODS AND RESULTS One hundred and nineteen uremic patients on hemodialysis and 57 control subjects with moderate-to-high cardiovascular risk factors and without chronic kidney disease (CKD) were enrolled. We used ultrasound to measure flow-mediated vasodilation (FMD). An AGE reader measured skin autoflurorescence (AF). We then compared differences in FMD and skin AF values between the two groups. The uremic subjects had significantly higher levels of skin AF (3.47±0.76 AU vs. 2.21±0.45 arbitrary units; P<0.01) and significantly lower levels of FMD (4.79%±1.88% vs. 7.19%±2.17%; P<0.01) than the non-CKD subjects. After adjusting for all potential covariates, we found that skin AF level independently predicted FMD in both the hemodialysis and the non-CKD groups. In the hemodialysis group, skin AF ≥ 3.05 arbitrary units predicted abnormal FMD at a sensitivity of 87.9% and a specificity of 78.6% (P<0.01). CONCLUSIONS Skin AF could be a useful marker to predict endothelial dysfunction in uremic subjects on hemodialysis.
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Affiliation(s)
- Chun-Cheng Wang
- Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan
- Division of Cardiology, Department of Internal Medicine, Taichung Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, Taichung, Taiwan
- Cardiovascular research laboratory, China Medical University Hospital, Taichung, Taiwan
| | - Yao-Chang Wang
- Division of Cardiothoracic surgery, Chang Gung Memorial Hospital Keelung Branch, Keelung, Taiwan
| | - Guei-Jane Wang
- Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan
- Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
- Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan
| | - Ming-Yi Shen
- Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan
| | - Yen-Lin Chang
- Department of Biomedical Engineering, Chun Yuan Christian University, Taoyuan, Taiwan
| | - Show-Yih Liou
- Formosan Blood Purification Foundation, Taipei, Taiwan
| | - Hung-Chih Chen
- Division of Nephrology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Chiz-Tzung Chang
- Division of Nephrology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- College of Medicine, China Medical University, Taichung, Taiwan
- Cardiovascular research laboratory, China Medical University Hospital, Taichung, Taiwan
- * E-mail:
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Yamanaka M, Shirakawa JI, Ohno RI, Shinagawa M, Hatano K, Sugawa H, Arakawa S, Furusawa C, Nagai M, Nagai R. Soft-shelled turtle eggs inhibit the formation of AGEs in the serum and skin of diabetic rats. J Clin Biochem Nutr 2016; 58:130-4. [PMID: 27013779 PMCID: PMC4788400 DOI: 10.3164/jcbn.15-131] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2015] [Accepted: 11/01/2015] [Indexed: 11/22/2022] Open
Abstract
Although soft-shelled turtle eggs (STE) have been used as a folk medicine for revitalization and the prevention of lifestyle-related diseases, the scientific evidence to support the use of STE in this manner is scarce. To clarify the physiological evidence, STE was administered to diabetic rats and the inhibitory effects on the formation of advanced glycation end-products (AGEs), which are known to increase with the progression of lifestyle-related diseases, were examined. STE and citric acid were administered to diabetic rats for 3 months, and serum Nε-(carboxymethyl)lysine (CML) contents were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Although the administration of STE did not affect the body weight, glycoalbumin or ketone body levels, it significantly reduced the serum level of CML. The accumulation of AGEs, which was measured by fluorescence intensity in the auricle skin and the lower gums, was also reduced by the administration of STE to a similar extent to that observed with citric acid. This report provides the first evidence that the oral administration of STE reduces the formation of AGEs, suggesting that one of the health effects of STE may be the inhibition of AGEs formation.
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Affiliation(s)
- Mikihiro Yamanaka
- Laboratory of Food and Regulation Biology, Graduate School of Agriculture, Tokai University, Kawayou, Minamiaso, Aso-gun, Kumamoto 869-1404, Japan; Healthcare Business Development Department I, Medical and Healthcare Business Development Unit, Business Solution Company, SHARP Corporation, 2613-1 Ichinomoto-cho, Tenri, Nara 632-8567, Japan
| | - Jun-Ichi Shirakawa
- Laboratory of Food and Regulation Biology, Graduate School of Agriculture, Tokai University, Kawayou, Minamiaso, Aso-gun, Kumamoto 869-1404, Japan
| | - Rei-Ichi Ohno
- Laboratory of Food and Regulation Biology, Graduate School of Agriculture, Tokai University, Kawayou, Minamiaso, Aso-gun, Kumamoto 869-1404, Japan
| | - Masatoshi Shinagawa
- Laboratory of Food and Regulation Biology, Graduate School of Agriculture, Tokai University, Kawayou, Minamiaso, Aso-gun, Kumamoto 869-1404, Japan
| | - Kota Hatano
- Laboratory of Food and Regulation Biology, Graduate School of Agriculture, Tokai University, Kawayou, Minamiaso, Aso-gun, Kumamoto 869-1404, Japan
| | - Hikari Sugawa
- Laboratory of Food and Regulation Biology, Graduate School of Agriculture, Tokai University, Kawayou, Minamiaso, Aso-gun, Kumamoto 869-1404, Japan
| | - Shoutaro Arakawa
- Laboratory of Food and Regulation Biology, Graduate School of Agriculture, Tokai University, Kawayou, Minamiaso, Aso-gun, Kumamoto 869-1404, Japan; Department of Orthopaedic Surgery, Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461, Japan
| | - Chisato Furusawa
- Laboratory of Food and Regulation Biology, Graduate School of Agriculture, Tokai University, Kawayou, Minamiaso, Aso-gun, Kumamoto 869-1404, Japan
| | - Mime Nagai
- Laboratory of Food and Regulation Biology, Graduate School of Agriculture, Tokai University, Kawayou, Minamiaso, Aso-gun, Kumamoto 869-1404, Japan
| | - Ryoji Nagai
- Laboratory of Food and Regulation Biology, Graduate School of Agriculture, Tokai University, Kawayou, Minamiaso, Aso-gun, Kumamoto 869-1404, Japan
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Choi EM, Suh KS, Kim YJ, Hong SM, Park SY, Chon S. Glabridin Alleviates the Toxic Effects of Methylglyoxal on Osteoblastic MC3T3-E1 Cells by Increasing Expression of the Glyoxalase System and Nrf2/HO-1 Signaling and Protecting Mitochondrial Function. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2016; 64:226-235. [PMID: 26670935 DOI: 10.1021/acs.jafc.5b05157] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/05/2023]
Abstract
Methylglyoxal (MG) contributes to the pathogenesis of age- and diabetes-associated complications. The present study investigated the effects of glabridin on MG-induced cytotoxicity in MC3T3-E1 osteoblastic cells. MC3T3-E1 cells were treated with glabridin in the presence of MG, and markers of mitochondrial function and oxidative damage were examined. Pretreatment of MC3T3-E1 osteoblastic cells with glabridin prevented MG-induced cell death, the production of intracellular reactive oxygen species and mitochondrial superoxides, cardiolipin peroxidation, and the production of inflammatory cytokines. The soluble form of receptor for advanced glycation end products (sRAGEs)/RAGE ratio increased upon MG treatment, but less so after pretreatment with glabridin, which also increased the level of reduced glutathione and the activities of glyoxalase I and heme oxygenase-1, all of which were reduced by MG. In addition, glabridin elevated the level of nuclear factor erythroid 2-related factor 2. These findings suggest that glabridin protects against MG-induced cell damage by inhibiting oxidative stress and increasing MG detoxification. Pretreatment of MC3T3-E1 osteoblastic cells with glabridin reduced MG-induced mitochondrial dysfunction. Additionally, the nitric oxide level significantly increased upon glabridin pretreatment. Together, these data show that glabridin may potentially serve to prevent the development of diabetic bone disease associated with MG-induced oxidative stress.
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Affiliation(s)
- Eun Mi Choi
- Department of Endocrinology & Metabolism, School of Medicine, Kyung Hee University , 1, Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea
| | - Kwang Sik Suh
- Research Institute of Endocrinology, Kyung Hee University Hospital , 1, Hoegi-dong, Dongdaemun-gu, Seoul 130-702, Republic of Korea
| | - Yu Jin Kim
- Department of Endocrinology & Metabolism, School of Medicine, Kyung Hee University , 1, Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea
| | - Soo Min Hong
- Department of Endocrinology & Metabolism, School of Medicine, Kyung Hee University , 1, Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea
- Department of Medicine, Graduate School, Kyung Hee University , Hoegi-dong, Dongdaemun-gu, Seoul 130-702, Republic of Korea
| | - So Yong Park
- Department of Endocrinology & Metabolism, School of Medicine, Kyung Hee University , 1, Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea
| | - Suk Chon
- Department of Endocrinology & Metabolism, School of Medicine, Kyung Hee University , 1, Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea
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Thiruvoipati T, Kielhorn CE, Armstrong EJ. Peripheral artery disease in patients with diabetes: Epidemiology, mechanisms, and outcomes. World J Diabetes 2015; 6:961-969. [PMID: 26185603 PMCID: PMC4499529 DOI: 10.4239/wjd.v6.i7.961] [Citation(s) in RCA: 237] [Impact Index Per Article: 23.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2014] [Revised: 11/20/2014] [Accepted: 04/02/2015] [Indexed: 02/05/2023] Open
Abstract
Peripheral artery disease (PAD) is the atherosclerosis of lower extremity arteries and is also associated with atherothrombosis of other vascular beds, including the cardiovascular and cerebrovascular systems. The presence of diabetes mellitus greatly increases the risk of PAD, as well as accelerates its course, making these patients more susceptible to ischemic events and impaired functional status compared to patients without diabetes. To minimize these cardiovascular risks it is critical to understand the pathophysiology of atherosclerosis in diabetic patients. This, in turn, can offer insights into the therapeutic avenues available for these patients. This article provides an overview of the epidemiology of PAD in diabetic patients, followed by an analysis of the mechanisms by which altered metabolism in diabetes promotes atherosclerosis and plaque instability. Outcomes of PAD in diabetic patients are also discussed, with a focus on diabetic ulcers and critical limb ischemia.
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Solís-Calero C, Ortega-Castro J, Frau J, Muñoz F. Nonenzymatic Reactions above Phospholipid Surfaces of Biological Membranes: Reactivity of Phospholipids and Their Oxidation Derivatives. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2015; 2015:319505. [PMID: 25977746 PMCID: PMC4419266 DOI: 10.1155/2015/319505] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/16/2014] [Revised: 03/24/2015] [Accepted: 03/25/2015] [Indexed: 01/03/2023]
Abstract
Phospholipids play multiple and essential roles in cells, as components of biological membranes. Although phospholipid bilayers provide the supporting matrix and surface for many enzymatic reactions, their inherent reactivity and possible catalytic role have not been highlighted. As other biomolecules, phospholipids are frequent targets of nonenzymatic modifications by reactive substances including oxidants and glycating agents which conduct to the formation of advanced lipoxidation end products (ALEs) and advanced glycation end products (AGEs). There are some theoretical studies about the mechanisms of reactions related to these processes on phosphatidylethanolamine surfaces, which hypothesize that cell membrane phospholipids surface environment could enhance some reactions through a catalyst effect. On the other hand, the phospholipid bilayers are susceptible to oxidative damage by oxidant agents as reactive oxygen species (ROS). Molecular dynamics simulations performed on phospholipid bilayers models, which include modified phospholipids by these reactions and subsequent reactions that conduct to formation of ALEs and AGEs, have revealed changes in the molecular interactions and biophysical properties of these bilayers as consequence of these reactions. Then, more studies are desirable which could correlate the biophysics of modified phospholipids with metabolism in processes such as aging and diseases such as diabetes, atherosclerosis, and Alzheimer's disease.
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Affiliation(s)
- Christian Solís-Calero
- Institut d'Investigació en Ciències de la Salut (IUNICS), Departament de Química, Universitat de les Illes Balears, 07122 Palma de Mallorca, Spain
- Instituto de Investigación Sanitaria de Palma, 07010 Palma, Spain
| | - Joaquín Ortega-Castro
- Institut d'Investigació en Ciències de la Salut (IUNICS), Departament de Química, Universitat de les Illes Balears, 07122 Palma de Mallorca, Spain
- Instituto de Investigación Sanitaria de Palma, 07010 Palma, Spain
| | - Juan Frau
- Institut d'Investigació en Ciències de la Salut (IUNICS), Departament de Química, Universitat de les Illes Balears, 07122 Palma de Mallorca, Spain
- Instituto de Investigación Sanitaria de Palma, 07010 Palma, Spain
| | - Francisco Muñoz
- Institut d'Investigació en Ciències de la Salut (IUNICS), Departament de Química, Universitat de les Illes Balears, 07122 Palma de Mallorca, Spain
- Instituto de Investigación Sanitaria de Palma, 07010 Palma, Spain
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Ergin V, Bali EB, Hariry RE, Karasu C. Natural products and the aging process. Horm Mol Biol Clin Investig 2015; 16:55-64. [PMID: 25436747 DOI: 10.1515/hmbci-2013-0031] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2013] [Accepted: 07/26/2013] [Indexed: 11/15/2022]
Abstract
Abstract Literature surveys show that the most of the research that have been conducted on the effect of herbal remedies on many tissue pathologies, including metabolic disturbances, cardiovascular decline, neurodegeneration, cataract, diabetic retinopathy and skin inflammation, all lead to an accelerated aging process. The increased carbonylation of proteins (carbonyl stress) disturbing their function has been indicated as an underlying mechanism of cellular senescence and age-related diseases. Because it is also linked to the carbonyl stress, aging chronic disease and inflammation plays an important role in understanding the clinical implications of cellular stress response and relevant markers. Greater knowledge of the molecular and cellular mechanisms involved in several pathologies associated with aging would provide a better understanding to help us to develop suitable strategies, use specific targets to mitigate the effect of human aging, prevent particularly chronic degenerative diseases and improve quality of life. However, research is lacking on the herbal compounds affecting cellular aging signaling as well as studies regarding the action mechanism(s) of natural products in prevention of the age-related disease. This review provides leads for identifying new medicinal agents or potential phytochemical drugs from plant sources for the prevention or delaying cellular aging processes and the treatment of some disorders related with accelerated body aging.
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