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Impaired functions of neural stem cells by abnormal nitric oxide-mediated signaling in an in vitro model of Niemann-Pick type C disease
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kim, Sun-Jung | - |
dc.contributor.author | Lim, Myung-Sin | - |
dc.contributor.author | Kang, Soo Kyung | - |
dc.contributor.author | Lee, Yong Soon | - |
dc.contributor.author | Kang, Kyung-Sun | - |
dc.date.accessioned | 2009-08-26T22:41:49Z | - |
dc.date.available | 2009-08-26T22:41:49Z | - |
dc.date.issued | 2008-04-08 | - |
dc.identifier.citation | Cell Res 2008; 18:686-694 | en |
dc.identifier.issn | 1001-0602 | - |
dc.identifier.uri | https://hdl.handle.net/10371/7890 | - |
dc.description.abstract | Nitric oxide (NO) has been implicated in the promotion of neurodegeneration. However, little is known about the relationship between NO and the self-renewal or differentiation capacity of neural stem cells (NSCs) in neurodegenerative disease. In this study, we investigated the effect of NO on self-renewal of NSCs in an animal model for Niemann-Pick type C (NPC) disease. We found that NO production was significantly increased in NSCs from NPC1-deficient mice (NPC1- /- ), which showed reduced NSC self-renewal. The number of nestin-positive cells and the size of neurospheres were both significantly decreased. The expression of NO synthase (NOS) was increased in neurospheres derived from the brain of NPC1- /- mice in comparison to wild-type neurospheres. NO-mediated activation of glycogen synthase kinase-3 (GSK3) and caspase-3 was also observed in NSCs from NPC1- /- mice. The self-renewal ability of NSCs from NPC1- /- mice was restored by an NOS inhibitor, L-NAME, which resulted in the inhibition of GSK3 and caspase-3. In addition, the differentiation ability of NSCs was partially restored and the number of Fluoro-Jade C-positive degenerating neurons was reduced. These data suggest that overproduction of NO in NPC disease impaired the self-renewal of NSCs. Control of NO production may be key for the treatment of NPC disease. | en |
dc.description.sponsorship | This work was supported by a grant from the Korean
Science & Engineering Foundation (R01-2005-000-10190-0) and the BK21 Program for Veterinary Science. | en |
dc.language.iso | en | en |
dc.publisher | Nature Publishing Group | en |
dc.subject | neural stem cells | en |
dc.subject | nitric oxide | en |
dc.subject | GSK3β | en |
dc.subject | Niemann-Pick type C1 disease | en |
dc.subject | caspase-3 | en |
dc.title | Impaired functions of neural stem cells by abnormal nitric oxide-mediated signaling in an in vitro model of Niemann-Pick type C disease | en |
dc.type | Article | en |
dc.contributor.AlternativeAuthor | 김선중 | - |
dc.contributor.AlternativeAuthor | 임명신 | - |
dc.contributor.AlternativeAuthor | 강수경 | - |
dc.contributor.AlternativeAuthor | 이영순 | - |
dc.contributor.AlternativeAuthor | 강경선 | - |
dc.identifier.doi | 10.1038/cr.2008.48 | - |
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