Abstract
In a cell-free apoptosis system, mitochondria spontaneously released cytochrome c, which activated DEVD-specific caspases, leading to fodrin cleavage and apoptotic nuclear morphology. Bcl-2 acted in situ on mitochondria to prevent the release of cytochrome c and thus caspase activation. During apoptosis in intact cells, cytochrome c translocation was similarly blocked by Bcl-2 but not by a caspase inhibitor, zVAD-fmk. In vitro, exogenous cytochrome c bypassed the inhibitory effect of Bcl-2. Cytochrome c release was unaccompanied by changes in mitochondrial membrane potential. Thus, Bcl-2 acts to inhibit cytochrome c translocation, thereby blocking caspase activation and the apoptotic process.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Chloromethyl Ketones / pharmacology
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Animals
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Apoptosis*
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Carrier Proteins / metabolism
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Cell Extracts
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Cell-Free System
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Cysteine Endopeptidases / metabolism
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Cysteine Proteinase Inhibitors / pharmacology
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Cytochrome c Group / metabolism*
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Cytosol / metabolism
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Membrane Potentials
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Microfilament Proteins / metabolism
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Mitochondria / metabolism*
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Ovum
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Proto-Oncogene Proteins c-bcl-2 / metabolism*
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Proto-Oncogene Proteins c-bcl-2 / pharmacology
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Recombinant Proteins
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Xenopus
Substances
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Amino Acid Chloromethyl Ketones
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Carrier Proteins
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Cell Extracts
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Cysteine Proteinase Inhibitors
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Cytochrome c Group
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Microfilament Proteins
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Proto-Oncogene Proteins c-bcl-2
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Recombinant Proteins
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benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
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fodrin
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Cysteine Endopeptidases