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Abstract
Inflammation enhanced by accumulation of reactive oxygen species plays an essential role in the progression of cardiovascular diseases. Using the 2D-oxyblot analysis and 2D-difference image gel electrophoresis (2D-DIGE), we compared the levels of ROS-induced carbonyl modification of myocardial proteins in the whole left ventricles between 6-week-old hamsters with dilated (TO-2) and hypertrophic cardiomyopathy (Bio14.6) and control hamsters (F1B). Then, 2D electrophoresis combined with MALDI-TOF/TOF tandem mass spectrometry detected 18 proteins with increased carbonyl level in cardiomyopathy hamsters compared with control hamster. Carbonyl modification of proteins related to ATP synthesis, including citric acid cycle and electron transport system, was observed in the hearts of hamsters with both types of cardiomyopathy. Further analysis indicated that left ventricular carbonyl production correlated negatively with succinyl-CoA:3-ketoacid-coenzyme A transferase 1 activity (r2 = 0.60, P = 0.0007) and ATP concentration (r2 = 0.29, P = 0.037), suggesting that protein carbonylation has negative effects on the levels of these biomolecules. Furthermore, carbonyl production significantly correlated with plasma Troponin T level (r2 = 0.33, P = 0.026). Reduction of energy metabolism by oxidative damage may contribute to the development of left ventricular impairment in cardiomyopathy.
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1 Graduate School of Regional Innovation Studies, Tsu, Japan; Department of Human Functional Genomics, Life Science Research Center, Mie University, Tsu, Japan; Department of Environmental and Preventive Medicine, Jichi Medical University School of Medicine, Shimotsuke, Japan
2 Graduate School of Regional Innovation Studies, Tsu, Japan; Community-University Research Cooperation Center, Mie University, Tsu, Japan
3 Graduate School of Regional Innovation Studies, Tsu, Japan; School of Public Health, Medical College of Soochow University, Suzhou, China
4 Department of Human Functional Genomics, Life Science Research Center, Mie University, Tsu, Japan
5 Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Japan