Nitric oxide and apoptosis: another paradigm for the double-edged role of nitric oxide

Apoptosis plays an important role in the development of the organism but also under various pathological conditions. Nitric oxide exhibits contradictory effects in the regulation of apoptosis. Both pro- and antiapoptotic effects have been demonstrated. The proapoptotic effects seem to be linked to pathophysiological conditions, where high amounts of NO are produced by the inducible nitric oxide synthase. In contrast, the continuous release of endothelial NO inhibits apoptosis and may contribute to the antiatherosclerotic function of NO. The present article summarizes these effects and provides insights into the role of NO in apoptotic signal transduction, with special regard to the Bcl-2 homologous proteins, the protease family of caspases and heat shock proteins.