Blocking cytochrome c activity within intact neurons inhibits apoptosis

被引:145
作者
Neame, SJ
Rubin, LL
Philpott, KL
机构
[1] UCL, Eisai London Res Labs, London WC1E 6BT, England
[2] Ontogeny Inc, Cambridge, MA 02138 USA
[3] SmithKline Beecham, Harlow CM19 5AW, Essex, England
关键词
cytochrome c; mitochondria; neuron; apoptosis; cAMP;
D O I
10.1083/jcb.142.6.1583
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:1583 / 1593
页数:11
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