BCL-2 PREVENTS NITRIC OXIDE-MEDIATED APOPTOSIS AND POLY(ADP-RIBOSE) POLYMERASE CLEAVAGE

Toxic effects of nitric oxide (NO) were suggested to be mediated by it s metabolite peroxynitrite, a strong oxidizing agent. To determine if antioxidative effects of Bcl-2 protooncogene can prevent NO-mediated a poptosis, we used vaccinia virus recombinants expressing mouse inducib le NO-synthase, iNOS, or human bcl-2 genes, Expression of iNOS in HeLa G cells induces apoptosis which can be prevented by co-expression of bcl-2 or by addition of reduced glutathione or N-acetylcysteine. We de monstrate that this NO-induced apoptosis proceeds through the activati on of interleukin-1 beta-converting enzyme-like proteases and cleavage of the poly(ADP-ribose) polymerase, an effect which is also prevented by Bcl-2. (C) 1997 Federation of European Biochemical Societies.