Dominant-negative c-Jun promotes neuronal survival by reducing BIM expression and inhibiting mitochondrial cytochrome c release

被引:521
作者
Whitfield, J
Neame, SJ
Paquet, L
Bernard, O
Ham, J
机构
[1] UCL, Eisai London Res Labs, London WC1E 6BT, England
[2] McGill Univ, Montreal Neurol Inst, Ctr Neuronal Survival, Montreal, PQ H3A 2B4, Canada
[3] Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia
基金
英国惠康基金;
关键词
D O I
10.1016/S0896-6273(01)00239-2
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Sympathetic neurons require nerve growth factor for survival and die by apoptosis in its absence. Key steps in the death pathway include c-Jun activation, mitochondrial cytochrome c release, and caspase activation. Here, we show that neurons rescued from NGF withdrawal-induced apoptosis by expression of dominant-negative c-Jun do not release cytochrome c from their mitochondria. Furthermore, we find that the mRNA for BIMEL, a proapoptotic BCL-2 family member, increases in level after NGF withdrawal and that this is reduced by dominant-negative c-Jun. Finally, overexpression of BIMEL in neurons induces cytochrome c redistribution and apoptosis in the presence of NGF, and neurons injected with sim antisense oligonucleotides or isolated from Bim(-/-) knockout mice die more slowly after NGF withdrawal.
引用
收藏
页码:629 / 643
页数:15
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