c-Jun N-terminal kinases trigger both degeneration and neurite outgrowth in primary hippocampal and cortical neurons.
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.
Eminel
S
S
Institute of Pharmacology, Universitaetsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Roemer
L
L
Waetzig
V
V
Herdegen
T
T
D000818:Animals; D000831:Animals, Newborn; D000873:Anthracenes / Q000494:pharmacology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009410:Nerve Degeneration / Q000201:enzymology* / Q000473:pathology; D016501:Neurites / Q000201:enzymology*; D009474:Neurons / Q000166:cytology / Q000201:enzymology*; D051381:Rats; D011921:Rats, Inbred WKY
D000873:Anthracenes; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases