الفهرس | Only 14 pages are availabe for public view |
Abstract Diabetic cardiomyopathy has been documented as an underlying etiology ofheart failure among diabetics. Although oxidative stress has been proposed to contribute to diabetic cardiomyopathy, much of the evidence lacks specificity. Furthermore, whether alterations occur at the cardiac proteome level in diabetic cardiac complications with attendant oxidative stress remains unknown. Therefore, we sought to identify cardiac protein changes in relation to myocardial oxidative stress that are specific to diabetic cardiomyopathy. Animal model of type 2 diabetes (OLETF rat) was used to investigate the alteration of myocardial proteome in diabetic cardiomyopathy. OLETF rats were examined for diabetic cardiomyopathy at 35 weeks of age by histopathogical and histochemical analyses. Myocardial oxidative stress was shown in diabetic rats, as indexed by significant increase in mitochondrial superoxide formation. In-depth mining of the diabetic myocardial proteome by proteomic analysis utilizing two-dimensional gel electrophoresis and mass spectrometry (2DE/MS) techniques revealed down-regulation of antioxidant and anti-apoptotic proteins and up-regulation of fatty acid oxidation related proteins in diabetic hearts. These results characterize a role of substrate switch to fatty acid utilization in alteration of metabolic pathways in diabetic cardiomyopathy. |