Bcl-2 prevents caspase-independent cell death.
Nitric oxide (NO) is implicated in apoptosis and has both cytotoxic and cytoprotective effects. Exogenous NO induced the death of PC12 and HeLa cells via a process showing features of both apoptosis and necrosis, with chromatin condensation, nuclear compaction, and mitochondrial swelling. Activation of caspases was not observed during NO-induced cell death. In addition, cell death was not inhibited by peptide caspase inhibitors or by expression of p35, a baculovirus-encoded caspase inhibitor, indicating that NO-induced cell death was independent of caspases. NO-induced cell death was enhanced by Bax expression in a caspase-independent manner and prevented by the anti-cell death protein Bcl-2. Although Bcl-2 has previously been shown to prevent cell death by inhibiting caspase activation, these results indicate that it can also prevent cell death via a caspase-independent mechanism.
Okuno
S
S
The First Department of Surgery, Biomedical Research Center, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565-0871 Japan.
Shimizu
S
S
Ito
T
T
Nomura
M
M
Hamada
E
E
Tsujimoto
Y
Y
Matsuda
H
H
D000310:Adrenal Gland Neoplasms; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D051379:Mice; D009336:Necrosis; D009569:Nitric Oxide / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology; D016716:PC12 Cells; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D010673:Pheochromocytoma; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology*; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D026423:S-Nitroso-N-Acetylpenicillamine; D014162:Transfection; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; C494827:Bax protein, mouse; C494828:Bax protein, rat; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D009842:Oligopeptides; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; C108637:aspartyl-glutamyl-valyl-aspartal; D051028:bcl-2-Associated X Protein; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D010396:Penicillamine