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 its metabolite peroxynitrite, a strong oxidizing agent. To determine if antioxidative effects of Bcl-2 protooncogene can prevent NO-mediated apoptosis, we used vaccinia virus recombinants expressing mouse inducible 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 demonstrate that this NO-induced apoptosis proceeds through the activation 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.
Mĕlková
Z
Z
Department of Biochemistry, SUNY, Brooklyn 11203, USA.
Lee
S B
SB
Rodriguez
D
D
Esteban
M
M
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D020170:Caspase 1; D002712:Chlorides / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D015870:Gene Expression; D019254:Genes, bcl-2 / Q000235:genetics; D005822:Genetic Vectors; D005978:Glutathione / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D007544:Isopropyl Thiogalactoside; D015227:Lipid Peroxidation; D051379:Mice; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000235:genetics; D011065:Poly(ADP-ribose) Polymerases / Q000096:biosynthesis* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014616:Vaccinia virus / Q000254:growth & development; D017967:Zinc Compounds / Q000494:pharmacology
D002712:Chlorides; D019253:Proto-Oncogene Proteins c-bcl-2; D017392:Thiobarbituric Acid Reactive Substances; D017967:Zinc Compounds; D009569:Nitric Oxide; D007544:Isopropyl Thiogalactoside; C016837:zinc chloride; D004247:DNA; D019001:Nitric Oxide Synthase; D011065:Poly(ADP-ribose) Polymerases; D003546:Cysteine Endopeptidases; D020170:Caspase 1; D005978:Glutathione; D000111:Acetylcysteine