c-Jun N-terminal kinases trigger both degeneration and neurite outgrowth in primary hippocampal and cortical neurons
Article first published online: 18 AUG 2008
© 2007 The Authors Journal Compilation © 2007 International Society for Neurochemistry
Journal of Neurochemistry
Volume 104, Issue 4, pages 957–969, February 2008
How to Cite
Eminel, S., Roemer, L., Waetzig, V. and Herdegen, T. (2008), c-Jun N-terminal kinases trigger both degeneration and neurite outgrowth in primary hippocampal and cortical neurons. Journal of Neurochemistry, 104: 957–969. doi: 10.1111/j.1471-4159.2007.05101.x
- Issue published online: 18 AUG 2008
- Article first published online: 18 AUG 2008
- Received May 10, 2007; revised manuscript received August 31, 2007; accepted September 24, 2007.
- mitogen-activated protein kinase;
We provide a comprehensive analysis on c-Jun N-terminal kinase (JNK) actions leading to death or differentiation in postnatal hippocampal and cortical neurons. Stimulation with glutamate or 6-hydroxy-dopamine caused activation of caspase-3 and apoptotic neuronal death which were both attenuated by JNK-inhibition. In cortical neurons, stress-induced nuclear JNK distribution was rather complex. We observed a decrease of activated and total JNK in the nucleus after stimulation, but an increase of the phosphorylated transcription factor c-Jun. Isoform-analysis revealed a nuclear translocation of JNK2, while nuclear protein levels of JNK1 decreased. This activation pattern differed from neurite formation. In hippocampal and cortical neurons, JNK activity continuously increased during neuritogenesis, whereas levels of phosphorylated c-Jun gradually declined. Despite these similarities, JNK inhibition by SP600125 only affected neurite outgrowth in hippocampal cells. Furthermore, experiments in JNK-deficient mice demonstrated that all JNK isoforms contributed to neuritogenesis. Summarizing, JNKs are involved in both neuritogenesis and death of primary neurons with differentially regulated nuclear translocation of specific isoforms after degenerative stress, while neuritogenesis is supported by all JNK isoforms.