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Neuronal NOS Induces Neuronal Differentiation Through a PKC alpha-Dependent GSK3 beta Inactivation Pathway in Hippocampal Neural Progenitor Cells

Title
Neuronal NOS Induces Neuronal Differentiation Through a PKC alpha-Dependent GSK3 beta Inactivation Pathway in Hippocampal Neural Progenitor Cells
Author
한중수
Keywords
Hippocampal neural progenitor cells; nNOS; NO; Cyclosporin A; PKCa alpha; GSK3 beta
Issue Date
2017-08
Publisher
SPRINGER
Citation
MOLECULAR NEUROBIOLOGY, v. 54, no. 7, page. 5646-5656
Abstract
We investigated the role of neuronal nitric oxide synthase (nNOS) in the neuronal differentiation of neural progenitor cells (NPCs) from hippocampi of E16.5 rat embryos. The production of nitric oxide (NO) and nNOS expression increased markedly during neuronal differentiation as did the expression of neurotrophin-3 (NT3), neurotrophin-4/5 (NT 4/5), and synapsin I. nNOS siRNA or the nNOS inhibitor, 7-nitroindazole (7-NI), decreased expression of the neurotrophins and synapsin I, and suppressed neurite outgrowth. These results suggest that nNOS plays a critical role in neuronal differentiation of hippocampal NPCs. nNOS-mediated neuronal differentiation is controlled by calcineurin since cyclosporin A (CsA), a calcineurin inhibitor, decreased nNOS activation and NO production, and inhibited neurite outgrowth. We found that inactivation of glycogen synthase kinase-3 beta (GSK3 beta) resulting from activation of protein kinase C alpha (PKC alpha) is involved in the nNOS-mediated neuronal differentiation. Moreover, lithium chloride (LiCl), a GSK3 beta inhibitor, increased neuronal differentiation by inhibiting the proliferation of NPCs. Taken together, these results suggest that neuronal differentiation is dependent on calcineurin-mediated activation of nNOS; this induces PKC alpha-dependent inactivation of GSK3 beta, which leads to inhibition of the proliferation of hippocampal NPCs.
URI
https://link.springer.com/article/10.1007%2Fs12035-016-0110-1https://repository.hanyang.ac.kr/handle/20.500.11754/115262
ISSN
0893-7648; 1559-1182
DOI
10.1007/s12035-016-0110-1
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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