Simulated hyperglycemia in rat cardiomyocytes: A proteomics approach for improved analysis of cellular alterations

Diabetic hyperglycemia can lead to stress‐related cellular apoptosis of cardiac tissue. However, the mechanism by which hyperglycemia inflicts this damage on the structure and function of the heart is unclear. In this study, we examined the relationship between proteome alterations, mitochondrial function, and major biochemical and electrophysiological changes affecting cardiac performance during simulated short‐term hyperglycemia. Two‐dimensional comparative proteomics analysis of rat hearts perfused with glucose at high (30 mM) or control (5.5 mM) levels revealed that glucose loading alters cardiomyocyte proteomes. It increased expression levels of initial enzymes of the tricarboxylic acid cycle, and of enzymes of fatty acid β‐oxidation, with consequent up‐regulation of enzymes of mitochondrial electron transport. It also markedly decreased expression of enzymes of glycolysis and the final steps of the tricarboxylic acid cycle. Glucose loading increased the rate of Bax‐independent apoptosis. High glucose increased the duration of the action potential and elevated level of intracellular cytoplasmic calcium. Surprisingly, glucose loading did not influence levels of nitric oxide or mitochondrial superoxide in isolated cardiomyocytes. In summary, short‐term simulated hyperglycemia attenuated expression of many anti‐apoptotic proteins. This effect was apparently mediated via alterations in multiple biochemical pathways that collectively increased apoptotic susceptibility.

[1]  J. McNeill,et al.  Antioxidant N-acetylcysteine restores myocardial Mn-SOD activity and attenuates myocardial dysfunction in diabetic rats. , 2006, European journal of pharmacology.

[2]  S. Fulda,et al.  Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy , 2006, Oncogene.

[3]  M. Donath,et al.  High glucose alters cardiomyocyte contacts and inhibits myofibrillar formation. , 2006, The Journal of clinical endocrinology and metabolism.

[4]  S. Nadtochiy,et al.  Different mechanisms of mitochondrial proton leak in ischaemia/reperfusion injury and preconditioning: implications for pathology and cardioprotection. , 2006, The Biochemical journal.

[5]  A. Scutt,et al.  Glucose-induced replicative senescence in mesenchymal stem cells. , 2006, Rejuvenation research.

[6]  L. Missiaen,et al.  The suppressor domain of inositol 1,4,5-trisphosphate receptor plays an essential role in the protection against apoptosis. , 2006, Cell calcium.

[7]  I. Poornima,et al.  Diabetic cardiomyopathy: the search for a unifying hypothesis. , 2006, Circulation research.

[8]  Jin Han,et al.  Potential biomarkers for ischemic heart damage identified in mitochondrial proteins by comparative proteomics , 2006, Proteomics.

[9]  M. Yorek,et al.  Oxidative-nitrosative stress and poly(ADP-ribose) polymerase (PARP) activation in experimental diabetic neuropathy: the relation is revisited. , 2005, Diabetes.

[10]  D. Allen,et al.  Mechanisms of high glucose-induced apoptosis and its relationship to diabetic complications. , 2005, The Journal of nutritional biochemistry.

[11]  A. Wein,et al.  Over expression of smooth muscle thin filament associated proteins in the bladder wall of diabetics. , 2005, The Journal of urology.

[12]  R. Hayward Stress , 2005, The Lancet.

[13]  M. Ikeda-Saito,et al.  Reversible redox-dependent modulation of mitochondrial aconitase and proteolytic activity during in vivo cardiac ischemia/reperfusion , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[14]  A. Jovanovic,et al.  High glucose regulates the activity of cardiac sarcolemmal ATP-sensitive K+ channels via 1,3-bisphosphoglycerate: a novel link between cardiac membrane excitability and glucose metabolism. , 2005, Diabetes.

[15]  D. Mcmaster,et al.  High glucose mediates pro‐oxidant and antioxidant enzyme activities in coronary endothelial cells , 2004, Diabetes, obesity & metabolism.

[16]  F. Natividad,et al.  Gender-specific proteomic alterations in glycolytic and mitochondrial pathways in aging monkey hearts. , 2004, Journal of molecular and cellular cardiology.

[17]  M. Lucas,et al.  High Glucose Levels Down-Regulate Glucose Transporter Expression That Correlates With Increased Oxidative Stress in Placental Trophoblast Cells IN Vitro , 2004, The Journal of the Society for Gynecologic Investigation: JSGI.

[18]  Brian O'Rourke,et al.  Synchronized Whole Cell Oscillations in Mitochondrial Metabolism Triggered by a Local Release of Reactive Oxygen Species in Cardiac Myocytes* , 2003, Journal of Biological Chemistry.

[19]  Y. Guiot,et al.  Haeme-oxygenase 1 expression in rat pancreatic beta cells is stimulated by supraphysiological glucose concentrations and by cyclic AMP , 2003, Diabetologia.

[20]  J. Olzmann,et al.  High glucose‐induced oxidative stress and mitochondrial dysfunction in neurons , 2002, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[21]  Jin Han,et al.  ATP-sensitive K(+) channel activation by nitric oxide and protein kinase G in rabbit ventricular myocytes. , 2002, American journal of physiology. Heart and circulatory physiology.

[22]  D. Sgroi,et al.  Increased expression of antioxidant and antiapoptotic genes in islets that may contribute to beta-cell survival during chronic hyperglycemia. , 2002, Diabetes.

[23]  J. Starnes,et al.  Effects of body temperature during exercise training on myocardial adaptations. , 2001, American journal of physiology. Heart and circulatory physiology.

[24]  S. Minotti,et al.  Mutant Cu/Zn-Superoxide Dismutase Proteins Have Altered Solubility and Interact with Heat Shock/Stress Proteins in Models of Amyotrophic Lateral Sclerosis* , 2001, The Journal of Biological Chemistry.

[25]  Y. Kaneda,et al.  Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage , 2000, Nature.

[26]  D. Hochstrasser,et al.  Modeling peptide mass fingerprinting data using the atomic composition of peptides , 1999, Electrophoresis.

[27]  S. Haffner,et al.  Effects of Diabetes and Level of Glycemia on All-Cause and Cardiovascular Mortality: The San Antonio Heart Study , 1998, Diabetes Care.

[28]  D. Severson,et al.  Type I and II models of diabetes produce different modifications of K+ currents in rat heart: role of insulin , 1998, The Journal of physiology.

[29]  J. Phillips,et al.  Targeted Overexpression of Cu/Zn Superoxide Dismutase Protects Pancreatic β-Cells Against Oxidative Stress , 1997, Diabetes.

[30]  G. King,et al.  Characterization of protein kinase C beta isoform activation on the gene expression of transforming growth factor-beta, extracellular matrix components, and prostanoids in the glomeruli of diabetic rats. , 1997, The Journal of clinical investigation.

[31]  J. Russell,et al.  Regulation of intracellular Ca2+ in the heart during diabetes. , 1997, Cardiovascular research.

[32]  J. McNeill,et al.  Intracellular calcium levels are unchanged in the diabetic heart. , 1997, Cardiovascular research.

[33]  F. Frerman,et al.  Three-dimensional structure of human electron transfer flavoprotein to 2.1-A resolution. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[34]  Sookja K. Chung,et al.  Demonstration that polyol accumulation is responsible for diabetic cataract by the use of transgenic mice expressing the aldose reductase gene in the lens. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[35]  B. Chandrasekar,et al.  Effects of n−3 and n−6 fatty acids on the activities and expression of hepatic antioxidant enzymes in autoimmune-prone NZB×NZW F1 mice , 1994, Lipids.

[36]  P. Jourdon,et al.  Calcium and potassium currents in ventricular myocytes isolated from diabetic rats. , 1993, The Journal of physiology.

[37]  M. Sutton,et al.  Information on type 1 diabetes mellitus and QT interval from identical twins. , 1993, The American journal of cardiology.

[38]  Zhengfeng Zhou,et al.  Na(+)‐Ca2+ exchange current in latent pacemaker cells isolated from cat right atrium. , 1993, The Journal of physiology.

[39]  P. Poole‐Wilson,et al.  Pathogenesis of Congestive State in Chronic Obstructive Pulmonary Disease: Studies of Body Water and Sodium, Renal Function, Hemodynamics, and Plasma Hormones During Edema and After Recovery , 1992, Circulation.

[40]  M. L’Abbé,et al.  Dietary (n-3) fatty acids affect rat heart, liver and aorta protective enzyme activities and lipid peroxidation. , 1991, The Journal of nutrition.

[41]  P. Kubes,et al.  Nitric oxide: an endogenous modulator of leukocyte adhesion. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[42]  K. Kako,et al.  Sensitivity to oxidants of mitochondrial and sarcoplasmic reticular calcium uptake in saponin-treated cardiac myocytes , 1989, Basic Research in Cardiology.

[43]  A. Hassid,et al.  Nitric oxide-generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. , 1989, The Journal of clinical investigation.

[44]  M. Marletta,et al.  Macrophage synthesis of nitrite, nitrate, and N-nitrosamines: precursors and role of the respiratory burst. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[45]  J. Hibbs,et al.  Macrophage cytotoxicity: role for L-arginine deiminase and imino nitrogen oxidation to nitrite. , 1987, Science.

[46]  A. Cerami,et al.  Aminoguanidine prevents diabetes-induced arterial wall protein cross-linking. , 1986, Science.

[47]  H. Beinert,et al.  A new iron-sulfur flavoprotein of the respiratory chain. A component of the fatty acid beta oxidation pathway. , 1977, The Journal of biological chemistry.

[48]  G. W. Beeler,et al.  Reconstruction of the action potential of ventricular myocardial fibres , 1977, The Journal of physiology.

[49]  Xianzhong Xiao,et al.  Heat shock pretreatment inhibited the release of Smac/DIABLO from mitochondria and apoptosis induced by hydrogen peroxide in cardiomyocytes and C2C12 myogenic cells , 2005, Cell stress & chaperones.

[50]  T. Lu,et al.  Heat shock treatment protects osmotic stress–induced dysfunction of the blood-brain barrier through preservation of tight junction proteins , 2004, Cell stress & chaperones.

[51]  M. Brownlee,et al.  Advanced protein glycosylation in diabetes and aging. , 1995, Annual review of medicine.

[52]  M. Toborek,et al.  Fatty acid-mediated effects on the glutathione redox cycle in cultured endothelial cells. , 1994, The American journal of clinical nutrition.

[53]  F. P. Altman Tetrazolium salts and formazans. , 1976, Progress in histochemistry and cytochemistry.

[54]  J. Vernier,et al.  DOSAGE DU GLYCOGÈENE HÉPATIQUE SUR COUPES À L'EPON EVALUATION QUANTITATIVE DU GLYCOGÈNE HÉPATIQUE PAR HISTOPHOTOMÉTRIE, SUR COUPES SEMI-FINES DE TISSU INCLUS DANS L'EPON , 1976 .

[55]  M. Brownlee Insight Review Articles , 2022 .