JNK3 contributes to c‐jun induction and apoptosis in 4‐hydroxynonenal‐treated sympathetic neurons

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Abstract
4-Hydroxynoneal (HNE), an end product of lipid peroxidation, induces apoptosis in many cell types, including neural cells. HNE toxicity is often accompanied by activation of the c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) pathway. Here we have evaluated the hypothesis that the primary JNK associated with neurons, JNK3, contributes to HNE-induced neuronal apoptosis. First, we demonstrate that HNE induces caspase-dependent apoptosis in sympathetic neurons. Second, we show that HNE-induced c-Jun phosphorylation and c-jun induction are attenuated in JNK3-deficient neurons. Third, we show that HNE neurotoxicity is significantly inhibited by JNK3 deficiency. In summary, these results indicate that JNK3 plays a critical role in HNE-induced c-Jun activation and apoptosis in sympathetic neurons.