Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adrenal Gland Neoplasms
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Animals
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Apoptosis / drug effects
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Apoptosis / physiology*
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Caspase 3
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Caspase Inhibitors
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Caspases / metabolism*
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Enzyme Inhibitors / pharmacology
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HeLa Cells
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Humans
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Kinetics
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Mice
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Necrosis
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Nitric Oxide / physiology
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Oligopeptides / pharmacology
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PC12 Cells
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Penicillamine / analogs & derivatives
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Penicillamine / pharmacology
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Pheochromocytoma
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / physiology
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / physiology*
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Rats
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Recombinant Proteins / metabolism
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S-Nitroso-N-Acetylpenicillamine
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Transfection
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bcl-2-Associated X Protein
Substances
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BAX protein, human
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Bax protein, mouse
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Bax protein, rat
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Caspase Inhibitors
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Enzyme Inhibitors
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Oligopeptides
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Recombinant Proteins
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aspartyl-glutamyl-valyl-aspartal
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bcl-2-Associated X Protein
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Nitric Oxide
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S-Nitroso-N-Acetylpenicillamine
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CASP3 protein, human
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Casp3 protein, mouse
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Casp3 protein, rat
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Caspase 3
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Caspases
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Penicillamine