Correlation between NO-induced ATP depletion and cytotoxicity in PC12 cells

To ascertain whether NO-elicited cell death is mediated by decreased intracellular ATP, the effect of sodium nitroprusside (SNP), a NO-generator, on ATP content in PC12 cells was examined. After treatment with SNP, the ATP content in PC12 cells was found to decline in a time- and concentration-dependent manner. The decline of ATP content in PC12 cells caused by SNP was found to occur before the appearance of cytotoxicity estimated by MTT staining. In addition, the ATP content of neuronally differentiated PC12 cells, which has been shown to have a higher resistance to SNP than the undifferentiated cells (Nakamura et al., 1997), was less affected by SNP treatment than the undifferentiated cells. These findings suggest that reduction of intracellular ATP content may be one of the mechanisms responsible for the NO toxicity in PC12 cells.