c-Jun Amino-Terminal Kinase is Involved in Valproic Acid-Mediated Neuronal Differentiation of Mouse Embryonic NSCs and Neurite Outgrowth of NSC-Derived Neurons.
Valproic acid (VPA), an anticonvulsant and mood-stabilizing drug, can induce neuronal differentiation, promote neurite extension and exert a neuroprotective effect in central nervous system (CNS) injuries; however, comparatively little is known regarding its action on mouse embryonic neural stem cells (NSCs) and the underlying molecular mechanism. Recent studies suggested that c-Jun N-terminal kinase (JNK) is required for neurite outgrowth and neuronal differentiation during neuronal development. In the present study, we cultured mouse embryonic NSCs and treated the cells with 1 mM VPA for up to 7 days. The results indicate that VPA promotes the neuronal differentiation of mouse embryonic NSCs and neurite outgrowth of NSC-derived neurons; moreover, VPA induces the phosphorylation of c-Jun by JNK. In contrast, the specific JNK inhibitor SP600125 decreased the VPA-stimulated increase in neuronal differentiation of mouse embryonic NSCs and neurite outgrowth of NSC-derived neurons. Taken together, these results suggest that VPA promotes neuronal differentiation of mouse embryonic NSCs and neurite outgrowth of NSC-derived neurons. Moreover, JNK activation is involved in the effects of VPA stimulation.
Department of Orthopaedics, Tianjin Medical University General Hospital, No. 154 Anshan Road, Heping District, Tianjin, 300052, People's Republic of China.
Lu
L
Lu
Department of Orthopaedics, Tianjin Medical University General Hospital, No. 154 Anshan Road, Heping District, Tianjin, 300052, People's Republic of China.
Hengxing
H
Zhou
Department of Orthopaedics, Tianjin Medical University General Hospital, No. 154 Anshan Road, Heping District, Tianjin, 300052, People's Republic of China.
Bin
B
Pan
Key Laboratory of Immuno Microenvironment and Disease of the Educational Ministry of China, Department of Immunology, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin, 300070, People's Republic of China.
Xueying
X
Li
Key Laboratory of Immuno Microenvironment and Disease of the Educational Ministry of China, Department of Immunology, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin, 300070, People's Republic of China.
Zheng
Z
Fu
Department of Orthopaedics, Tianjin Medical University General Hospital, No. 154 Anshan Road, Heping District, Tianjin, 300052, People's Republic of China.
Jun
J
Liu
Department of Orthopaedics, Tianjin Medical University General Hospital, No. 154 Anshan Road, Heping District, Tianjin, 300052, People's Republic of China.
Zhongju
Z
Shi
Kosair Children's Hospital Research Institute at the Department of Pediatrics, University of Louisville School of Medicine, Louisville, KY, 40202, USA.
Tianci
T
Chu
Department of Orthopaedics, Tianjin Medical University General Hospital, No. 154 Anshan Road, Heping District, Tianjin, 300052, People's Republic of China.
Zhijian
Z
Wei
Department of Orthopaedics, Tianjin Medical University General Hospital, No. 154 Anshan Road, Heping District, Tianjin, 300052, People's Republic of China.
Guangzhi
G
Ning
Department of Orthopaedics, Tianjin Medical University General Hospital, No. 154 Anshan Road, Heping District, Tianjin, 300052, People's Republic of China. fshiqing1967@hotmail.com.
Shiqing
S
Feng
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000187:drug effects / Q000378:metabolism*; D000071446:Neuronal Outgrowth / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D014635:Valproic Acid / Q000494:pharmacology*
D000873:Anthracenes; C432165:pyrazolanthrone; D014635:Valproic Acid; D048031:JNK Mitogen-Activated Protein Kinases
JNK; Neural stem cells; Neurite outgrowth; Neuronal differentiation; Valproic acid