Nitric oxide inhibits execution of apoptosis at two distinct ATP-dependentsteps upstream and downstream of mitochondrial cytochrome c release

The endogenous mediator nitric oxide (NO) blocked apoptosis of Jurkat cells elicited by staurosporine, anti-CD95 or chemotherapeutics, and switched de ath to necrosis, The switch in the mode of cell death was dependent on the ATP loss elicited by NO. This affected two distinct steps of the apoptotic cascade. First, the release of cytochrome c from mitochondria was delayed b y NO. Second, processing of procaspases-3/7 to the active proteases was pre vented even after cytochrome c had been released. Thus, NO interferes with execution steps of apoptosis both upstream and downstream of cytochrome c r elease. (C) 1999 Academic Press.