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

J Whitfield, SJ Neame, L Paquet, O Bernard, J Ham - Neuron, 2001 - cell.com
J Whitfield, SJ Neame, L Paquet, O Bernard, J Ham
Neuron, 2001cell.com
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 …
Abstract
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 Bim antisense oligonucleotides or isolated from Bim−/− knockout mice die more slowly after NGF withdrawal.
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