Abstract
Sympathetic neurons undergoing programmed cell death after nerve growth factor (NGF) deprivation are shown to exhibit a protein synthesis-dependent, BAX-dependent loss of cytochrome c from the mitochondria. However, cytoplasmic microinjection of cytochrome c was insufficient to induce cell death in NGF-maintained sympathetic neurons. In contrast, microinjection of cytochrome c rapidly induced a caspase-dependent death in NGF-deprived, Bax-deficient or NGF-deprived, cycloheximide-treated neurons. Cells needed to be deprived of NGF for 15-20 hr before they acquired competence to die with injection of cytochrome c. These data suggest that NGF deprivation induced the translocation of cytochrome c and another event, which we term as competence-to-die, that was independent of macromolecular synthesis and BAX function. Both these processes were required for neurons to undergo apoptosis.
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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Caspases / physiology
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Cell Survival / drug effects
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Cell Survival / physiology
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Cells, Cultured
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Cycloheximide / pharmacology
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Cytochrome c Group / metabolism
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Cytochrome c Group / pharmacology*
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Cytoplasm / physiology*
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Dose-Response Relationship, Drug
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Mice
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Microinjections
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Mitochondria / metabolism
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Nerve Growth Factors / deficiency
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Nerve Growth Factors / pharmacology
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Nerve Tissue Proteins / biosynthesis
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Neurons / drug effects*
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Neurons / metabolism
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Neurons / physiology*
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Protein Synthesis Inhibitors / pharmacology
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Proto-Oncogene Proteins / deficiency
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-bcl-2*
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Superior Cervical Ganglion / cytology
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bcl-2-Associated X Protein
Substances
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Amino Acid Chloromethyl Ketones
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Bax protein, mouse
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Cytochrome c Group
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Nerve Growth Factors
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Nerve Tissue Proteins
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Protein Synthesis Inhibitors
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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bcl-2-Associated X Protein
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butyloxycarbonyl-O-methyl-aspartyl-fluoromethyl ketone
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Cycloheximide
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Caspases