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© The Rockefeller University Press, 0021-9525/1998//1583 $5.00
The Journal of Cell Biology, Volume 142, Number 6, , 1998 1583-1593

Regular Articles

Blocking Cytochrome c Activity within Intact Neurons Inhibits Apoptosis



Stephen J. Neame*, Lee L. Rubin{ddagger}, and Karen L. Philpott§

* Eisai London Research Laboratories, Bernard Katz Building, University College London, London WC1E 6BT, United Kingdom; {ddagger} Ontogeny Inc., Cambridge, Massachusetts 02138; and § SmithKline Beecham, New Frontiers Science Park, Harlow, Essex CM19 5AW, United Kingdom

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.

Key Words: cytochrome c • mitochondria • neuron • apoptosis • cAMP

Abbreviations used in this paper: Apaf, apoptotic protease activating factor; CPT-cAMP, 8-(4-chlorophenylthio)adenosine 3':5'-cyclic monophosphate; DEVD-AMC, Asp-Glu-Val-Asp-amino methyl coumarin; PKA, protein-dependent kinase A; SCG, superior cervical ganglia; ZVADfmk, Z-Val-Ala-Asp-fluoromethylketone; {Delta}{Psi}m, mitochondrial inner membrane potential.

Address all correspondence to Stephen J. Neame, Eisai London Research Laboratories, Bernard Katz Building, University College London, Gower Street, London WC1E 6BT, UK. Tel.: 0171 413 1130. Fax: 0171 413 1121. E-mail: sjneame{at}elrl.co.uk


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