Whitfield J, Neame S J, Paquet L, Bernard O, Ham J
Eisai London Research Laboratories, Bernard Katz Building, University College London, Gower Street, WC1E 6BT, London, United Kingdom.
Neuron. 2001 Mar;29(3):629-43. doi: 10.1016/s0896-6273(01)00239-2.
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 BIM(EL), 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 BIM(EL) in neurons induces cytochrome c redistribution and apoptosis in the presence of NGF, and neurons injected with Bim antisense oligonucleotides or isolated from Bim(-/-) knockout mice die more slowly after NGF withdrawal.
交感神经元的存活需要神经生长因子，缺乏该因子时会通过凋亡死亡。死亡途径中的关键步骤包括c-Jun激活、线粒体细胞色素c释放和半胱天冬酶激活。在此，我们表明，通过表达显性负性c-Jun从NGF撤除诱导的凋亡中挽救的神经元不会从其线粒体中释放细胞色素c。此外，我们发现促凋亡BCL-2家族成员BIM(EL)的mRNA在NGF撤除后水平升高，而显性负性c-Jun可使其降低。最后，在存在NGF的情况下，神经元中BIM(EL)的过表达诱导细胞色素c重新分布和凋亡，注射Bim反义寡核苷酸或从Bim(-/-)基因敲除小鼠分离的神经元在NGF撤除后死亡更慢。
