Nitric oxide can function as either a killer molecule or an antiapoptotic effector in cardiomyocytes

Caspase enzymes are a family of cysteine proteases that play a central role in apoptosis. Recently, it has been demonstrated that caspases can be S-ni trosylated and inhibited by nitric oxide (NO). The present report shows tha t in chick embryo heart cells (CEHC), NO donor molecules such as S-nitroso- N-acetylpenicillamine (SNAP), S-nitrosoglutathione, spermine-NO or sodium n itroprusside inhibit caspase activity in both basal and staurosporine-treat ed cells. However, the inhibitory effect of NO donors on caspase activity i s accompanied by a parallel cytotoxic effect, that precludes NO to exert it s antiapoptotic capability. N-Acetylcysteine (NAC) at a concentration of 10 mM blocks depletion of cellular glutathione and cell death in SNAP-treated CEHC, but it poorly affects the ability of SNAP to inhibit caspase activit y. Consequently, in the presence of NAG, SNAP attenuates not only caspase a ctivity but also cell death of staurosporine-treated CEHC. These data show that changes in the redox environment may inhibit NO-mediated toxicity, wit hout affecting the antiapoptotic capability of NO, mediated by inhibition o f caspase enzymes. NO may thus be transformed from a killer molecule into a n antiapoptotic agent. (C) 1999 Elsevier Science B.V. All rights reserved.