Nitric oxide damages neuronal mitochondria and induces apoptosis in neurons

The cytotoxic effect of nitric oxide on primarily cultured rat cerebellar g ranule cells was studied, and the mechanisms were discussed. The results sh owed that nitric oxide donor S-nitroso-N-acetyl-penicillamine (SNAP; 500 mu mol/L) could induce apoptosis in immature cultures of cerebellar granule c ells. Flow cytometry and HPLC analyses revealed that after treatment with S NAP, the mitochondrial transmembrane potential and the cellular ATP content decreased significantly. Nitric oxide scavenger hemoglobin could effective ly prevent the neuronal mitochondria from dysfunction and attenuate apoptos is. The results suggested that nitric oxide activated the apoptotic program by inhibiting the activity of mitochondrial respiratory chain and thus dec reasing the cellular ATP content.