c-Jun N-terminal kinase signaling regulates events associated with both health and degeneration in motoneurons.
The c-Jun N-terminal kinases (JNKs) are activated by various stimuli and are critical for neuronal development as well as for death following a stressful stimulus. Here, we have evaluated JNK activity in both healthy and dying motoneurons from developing chick embryos and found no apparent difference in overall JNK activity between the conditions, suggesting that this pathway maybe critical in both circumstances. Pharmacological inhibition of JNK in healthy motoneurons supplied with trophic support resulted in decreased mitochondrial membrane potential, neurite outgrowth, and phosphorylation of microtubule-associated protein 1B. On the other hand, in motoneurons deprived of trophic support, inhibition of JNK attenuated caspase activation, and nuclear condensation. We also examined the role of JNK's downstream substrate c-Jun in mediating these events. While c-Jun expression and phosphorylation were greater in cells supplied with trophic support as compared with those deprived, inhibition of c-Jun had no effect on nuclear condensation in dying cells or neurite outgrowth in healthy cells, suggesting that JNK's role in these events is independent of c-Jun. Together, our data underscore the dualistic nature of JNK signaling that is critical for both survival and degenerative changes in motoneurons.
Newbern
J
J
Department of Neurobiology and Anatomy, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA.
Taylor
A
A
Robinson
M
M
Lively
M O
MO
Milligan
C E
CE
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism*; D009410:Nerve Degeneration / Q000201:enzymology* / Q000503:physiopathology; D016501:Neurites / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D014162:Transfection
D000873:Anthracenes; D004791:Enzyme Inhibitors; D008869:Microtubule-Associated Proteins; C085284:microtubule-associated protein 1B; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases; D020169:Caspases