Blocking Cytochrome c Activity within Intact Neurons Inhibits Apoptosis

doi:10.1083/jcb.142.6.1583

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J. Cell Biol., Volume 142, Number 6, September 21, 1998 1583-1593

Blocking Cytochrome c Activity within Intact Neurons Inhibits Apoptosis

Stephen J. Neame,^* Lee L. Rubin, and Karen L. Philpott^§

^* Eisai London Research Laboratories, Bernard Katz Building, University College London, London WC1E 6BT, United Kingdom; 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 intactrat superior cervical ganglion (SCG) neurons, we observe the redistributionof cytochrome c from the mitochondria to the cytoplasm. This redistributionis not inhibited by the caspase inhibitor Z-Val-Ala-Asp-fluoromethylketone(ZVADfmk) but is blocked by either of the neuronal survival agents8-(4-chlorophenylthio)adenosine 3':5'-cyclic monophosphate (CPT-cAMP)or cycloheximide. Moreover, microinjection of SCG neurons withantibody to cytochrome c blocks NGF withdrawal-induced apoptosis.However, microinjection of SCG neurons with cytochrome c doesnot alter the rate of apoptosis in either the presence or absenceof NGF. These data suggest that cytochrome c is an intrinsic butnot limiting component of the neuronal apoptotic pathway.

Key words: cytochrome c; mitochondria; neuron; apoptosis; cAMP

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