Blocking cytochrome c activity within intact neurons inhibits apoptosis.
Cytochrome c has been shown to play a role in cell-free models of apoptosis. During NGF withdrawal-induced apoptosis of intact rat superior cervical ganglion (SCG) neurons, we observe the redistribution of cytochrome c from the mitochondria to the cytoplasm. This redistribution is not inhibited by the caspase inhibitor Z-Val-Ala-Asp-fluoromethylketone (ZVADfmk) but is blocked by either of the neuronal survival agents 8-(4-chlorophenylthio)adenosine 3':5'-cyclic monophosphate (CPT-cAMP) or cycloheximide. Moreover, microinjection of SCG neurons with antibody to cytochrome c blocks NGF withdrawal-induced apoptosis. However, microinjection of SCG neurons with cytochrome c does not alter the rate of apoptosis in either the presence or absence of NGF. These data suggest that cytochrome c is an intrinsic but not limiting component of the neuronal apoptotic pathway.
Neame
S J
SJ
Eisai London Research Laboratories, Bernard Katz Building, University College London, London WC1E 6BT, United Kingdom. sjneame@elrl.co.uk
Rubin
L L
LL
Philpott
K L
KL
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D001692:Biological Transport; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003574:Cytochrome c Group / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D007425:Intracellular Membranes / Q000502:physiology; D019169:Jurkat Cells; D008564:Membrane Potentials; D008845:Microinjections; D008928:Mitochondria / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D018696:Neuroprotective Agents / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017783:Superior Cervical Ganglion / Q000166:cytology; D013873:Thionucleotides / Q000494:pharmacology
D000590:Amino Acid Chloromethyl Ketones; D015853:Cysteine Proteinase Inhibitors; D003574:Cytochrome c Group; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D011500:Protein Synthesis Inhibitors; D013873:Thionucleotides; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D000255:Adenosine Triphosphate; D003513:Cycloheximide; D000242:Cyclic AMP