Hydrogen peroxide dose dependent induction of cell death or hypertrophy in cardiomyocytes.
Cardiomyocyte hypertrophy and cell death are often observed in the end stages of heart failure. The triggers of these two cellular processes are not known under most pathological conditions. Oxidants are by-products of aerobic metabolism. The level of oxidants increases as a result of ischemic reperfusion. Using H9C2 and primary cultured neonatal rat cardiomyocytes, we found that a 2-h pulse treatment with H(2)O(2) at 250 microM or lower caused activation of DEVD sequence specific caspases. The activity of DEVD-ase peaked with 200 microM H(2)O(2) at 24 h. While a fraction of the cells detached and showed nuclear condensation, the majority of the cells (>55%) survived the treatment and appeared to enlarge when cultured for 5 days. These cells showed increases in cell surface area, cell volume, and protein content. With 200 microM H(2)O(2), treated cells appeared to be six times bigger in volume and contained three times more protein per cell than untreated cells. The enlarged cells showed enhanced actin stress fibers and disrupted myofibrils. Our data indicate that while H(2)O(2) can cause cell death, the surviving cardiomyocytes undergo hypertrophy.
Chen
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QM
Department of Pharmacology, University of Arizona, Skaggs Pharmaceutical Science Building, 1703 East Mabel Street, Tucson, Arizona, 85721, USA. chen@pharmacy.arizona.edu
Tu
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Wu
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Bahl
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D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D006332:Cardiomegaly / Q000209:etiology / Q000473:pathology; D016923:Cell Death / Q000187:drug effects*; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000008:administration & dosage / Q000633:toxicity*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009218:Myosins / Q000378:metabolism; D009336:Necrosis; D051381:Rats
D000199:Actins; D006861:Hydrogen Peroxide; D009218:Myosins