Hydrogen peroxide dose dependent induction of cell death or hypertrophy incardiomyocytes

Cardiomyocyte hypertrophy and cell death are often observed in the end stag es of heart failure. The triggers of these two cellular processes are not k nown under most pathological conditions. Oxidants are byproducts of aerobic metabolism. The level of oxidants increases as a result of ischemic reperf usion, Using H9C2 and primary cultured neonatal rat cardiomyocytes, we foun d that a 2-h pulse treatment with H2O2 at 250 mu M or lower caused activati on of DEVD sequence specific caspases, The activity of DEVD-ase peaked with 200 mu M H2O2 at 24 h, While a fraction of the cells detached and showed n uclear condensation, the majority of the cells (>55%) survived the treatmen t and appeared to enlarge when cultured for 5 days. These cells showed incr eases in cell surface area, cell volume, and protein content. With 200 mu M H2O2, treated cells appeared to be six times bigger in volume and containe d three times more protein per cell than untreated cells. The enlarged cell s showed enhanced actin stress fibers and disrupted myofibrils. Our data in dicate that while H2O2 can cause cell death, the surviving cardiomyocytes u ndergo hypertrophy, (C) 2000 Academic Press.