Nitric-oxide-induced necrosis and apoptosis in PC12 cells mediated by mitochondria

Abstract: Nitric oxide (NO) can trigger either necrotic or apoptotic cell death. We have used PC12 cells to inves-tigate the extent to which NO-induced cell death is me-diated by mitochondria. Addition of NO donors, 1 mM S-nitroso-N-acetyl-DL-penicillamine (SNAP) or 1 mM di-ethylenetriamine–NO adduct (NOC-18), to PC12 cells re-sulted in a steady-state level of 1–3 mM NO, rapid and almost complete inhibition of cellular respiration (within 1 min), and a rapid decrease in mitochondrial membrane potential within the cells. A 24-h incubation of PC12 cells with NO donors (SNAP or NOC-18) or specific inhibitors of mitochondrial respiration (myxothiazol, rotenone, or azide), in the absence of glucose, caused total ATP de-pletion and resulted in 80–100 % necrosis. The presence of glucose almost completely prevented the decrease i