Gene expression of antioxidative enzymes in the human heart - Increased expression of catalase in the end-stage failing heart

Article

关键词: EXTRACELLULAR-SUPEROXIDE DISMUTASE;    FREE-RADICAL SYSTEM;    OXIDATIVE STRESS;    GLUTATHIONE-PEROXIDASE;    MYOCARDIAL-INFARCTION;    FAILURE SUBSEQUENT;    REPERFUSION INJURY;    ENDOTHELIAL-CELLS;    GUINEA-PIG;    ISCHEMIA;   

DOI  :  10.1161/01.CIR.101.1.33

来源: SCIE

【 摘 要 】

Background-An increase in oxidative stress is suggested to be intimately involved in the pathogenesis of heart failure. However, gene expression of enzymes that metabolize reactive oxygen metabolites has not been investigated in the human heart. Methods and Results-Myocardial tissue homogenates of the left ventricular wall from hearts in end-stage failure due to dilated (DCM) or ischemic (ICM) cardiomyopathy (n=12 each), as well as from nonfailing donor hearts (n=12), were analyzed for mRNA levels of manganese superoxide dismutase (MnSOD), copper-zinc superoxide dismutase (CuZnSOD), glutathione peroxidase (GPX), and catalase by Northern blot analyses. Protein levels of MnSOD, CuZnSOD, and catalase were determined by Western blot or ELISA. MnSOD, CuZnSOD, and GPX mRNA levels were similar in all 3 groups. In contrast, catalase mRNA levels were found to be increased by 123+/-23% in DCM hearts and by 93+/-10% in ICM hearts (P<0.01 each) compared with control hearts. Likewise, catalase protein levels were found to be increased in failing hearts (DCM by 90+/-10%, ICM by 90+/-13%; P<0.05 each) compared with control hearts. In addition, the observed upregulation of catalase mRNA and protein in failing hearts was attended by an increased catalase enzyme activity (DCM by 124+/-16%, ICM by 117+/-15%; P<0.01 each), whereas MnSOD, CuZnSOD, and GPX enzyme activity levels were unchanged in failing compared with nonfailing myocardium. Conclusions-Increased oxidative stress in human end-stage heart failure may result in a specific upregulation of catalase gene expression as a compensatory mechanism, whereas SOD and GPX gene expression remain unaffected.

【 授权许可】

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