Activation of c-Jun N-terminal kinase is required for neurite outgrowth of dopaminergic neuronal cells.
Recent studies indicate that activation of stress-activated protein kinases may be implicated in a broad range of biological activities including differentiation. To directly examine whether stress-activated protein kinases are involved in neuronal differentiation, we utilized retinoic acid-induced and spontaneous models of neurite outgrowth in dopaminergic neurons. Here, we show that retinoic acid-induced neurite outgrowth in MN9D dopaminergic neuronal cells was accompanied by activation of c-Jun N-terminal kinase but not p38. Consequently, cotreatment with a specific inhibitor of c-Jun N-terminal kinase or overexpression of c-Jun N-terminal kinase-binding domain of c-Jun N-terminal kinase-interacting protein-1 blocked retinoic acid-induced neurite outgrowth. In primary cultures of dopaminergic neurons, the extent of neurite outgrowth increased spontaneously in a time-dependent manner. When these cultures were treated with a specific inhibitor of c-Jun N-terminal kinase, the total extent of neurites, the primary neurite length and the number of neurites per cell were suppressed significantly. Thus, our data indicate that the c-Jun N-terminal kinase signal seems to play an important role during morphological differentiation in cultured dopaminergic neurons.
Eom
Dae-Seok
DS
Department of Biology, Yonsei University College of Science, Seoul 120-749, Korea.
Choi
Won-Seok
WS
Ji
Suena
S
Cho
Jin W
JW
Oh
Young J
YJ
D000704:Analysis of Variance; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D015153:Blotting, Western / Q000379:methods; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006825:Hybridomas; D007150:Immunohistochemistry / Q000379:methods; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism* / Q000502:physiology; D008636:Mesencephalon / Q000166:cytology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D014162:Transfection / Q000379:methods; D014212:Tretinoin / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D000873:Anthracenes; D004791:Enzyme Inhibitors; C432165:pyrazolanthrone; D014212:Tretinoin; D014446:Tyrosine 3-Monooxygenase; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D004298:Dopamine