JNK3 contributes to c-jun induction and apoptosis in 4-hydroxynonenal-treated sympathetic neurons.
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.
Bruckner
Shane R
SR
Department of Physiology, Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536, USA.
Estus
Steven
S
D000447:Aldehydes / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002478:Cells, Cultured; D015853:Cysteine Proteinase Inhibitors / Q000633:toxicity*; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D048057:Mitogen-Activated Protein Kinase 10; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics*; D051381:Rats; D017783:Superior Cervical Ganglion / Q000166:cytology*
D000447:Aldehydes; D015853:Cysteine Proteinase Inhibitors; D016755:Proto-Oncogene Proteins c-jun; D048057:Mitogen-Activated Protein Kinase 10; D011505:Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases; C027576:4-hydroxy-2-nonenal