Mitochondrial calpain-1 disrupts ATP synthase and induces superoxide generation in type-1 diabetic hearts: a novel mechanism contributing to diabetic cardiomyopathy Running title: Mitochondrial calpain-1 in diabetic cardiomyopathy

نویسندگان

  • Rui Ni
  • Dong Zheng
  • Sidong Xiong
  • David J Hill
  • Tao Sun
  • Richard B Gardiner
  • Chang Fan
  • Yanrong Lu
  • Dale Abel
  • Peter A Greer
  • Tianqing Peng
چکیده

1 From Institutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu Province, China 215123. 2 Lawson Health Research Institute, Departments of 3 Medicine, 4 Pathology, 5 Biology, University of Western Ontario, London, Ontario, Canada N6A 4G5. 6 Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH, USA 45267-0575. 7 Key Laboratory of Transplant Engineering and Immunology, Ministry of Health; Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China 610041. 8 Fraternal Order of Eagles Diabetes Research Center, Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242. 9 Division of Cancer Biology and Genetics, Queen's University Cancer Research Institute, Department of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, Canada K7L 3N6.

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Mitochondrial Calpain-1 Disrupts ATP Synthase and Induces Superoxide Generation in Type 1 Diabetic Hearts: A Novel Mechanism Contributing to Diabetic Cardiomyopathy

Calpain plays a critical role in cardiomyopathic changes in type 1 diabetes (T1D). This study investigated how calpain regulates mitochondrial reactive oxygen species (ROS) generation in the development of diabetic cardiomyopathy. T1D was induced in transgenic mice overexpressing calpastatin, in mice with cardiomyocyte-specific capn4 deletion, or in their wild-type littermates by injection of s...

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Deletion of capn4 Protects the Heart Against Endotoxemic Injury by Preventing ATP Synthase Disruption and Inhibiting Mitochondrial Superoxide Generation.

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Calpain activation contributes to hyperglycaemia-induced apoptosis in cardiomyocytes.

AIMS Cardiomyocyte apoptosis contributes to cardiac complications of diabetes. The aim of this study was to investigate the role of calpain in cardiomyocyte apoptosis induced by hyperglycaemia. METHODS AND RESULTS In cultured adult rat ventricular cardiomyocytes, high glucose (33 mM) increased calpain activity and induced apoptosis, concomitant with the impairment of Na+/K+ ATPase activity. T...

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Heart mitochondrial dysfunction in diabetic rats

Diabetic cardiomyopathy, i.e. the ventricular dysfunction in the absence of hypertension or coronary arterial disease, is a common complication of diabetes mellitus that leads to a heightened risk of heart failure and death among diabetic patients. This contractile dysfunction could be associated to mitochondrial dysfunction, in which mitochondrial biogenesis could emerge as a compensatory mech...

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Targeted Inhibition of Calpain Reduces Myocardial Hypertrophy and Fibrosis in Mouse Models of Type 1 Diabetes

OBJECTIVE Recently we have shown that calpain-1 activation contributes to cardiomyocyte apoptosis induced by hyperglycemia. This study was undertaken to investigate whether targeted disruption of calpain would reduce myocardial hypertrophy and fibrosis in mouse models of type 1 diabetes. RESEARCH DESIGN AND METHODS Diabetes in mice was induced by injection of streptozotocin (STZ), and OVE26 m...

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تاریخ انتشار 2015