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JNK3 contributes to c‐jun induction and apoptosis in 4‐hydroxynonenal‐treated sympathetic neurons
Author(s) -
Bruckner Shane R.,
Estus Steven
Publication year - 2002
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.10437
Subject(s) - 4 hydroxynonenal , neurotoxicity , apoptosis , c jun , kinase , microbiology and biotechnology , phosphorylation , downregulation and upregulation , chemistry , oxidative stress , lipid peroxidation , biology , toxicity , biochemistry , gene , transcription factor , organic chemistry
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. © 2002 Wiley‐Liss, Inc.