期刊
NEURAL REGENERATION RESEARCH
卷 9, 期 19, 页码 1770-1778出版社
SHENYANG EDITORIAL DEPT NEURAL REGENERATION RES
DOI: 10.4103/1673-5374.143421
关键词
nerve regeneration; neuroderegeneration; embryonic neural stem cells; adenosine monophosphate-activated protein kinase alpha; paired box 3; p53; SOD1(G93A) mouse; amyotrophic lateral sclerosis; oxidative stress; hydrogen peroxide; apoptosis; NSFC grants; neural regeneration
资金
- National Natural Sciences Foundation of China [81030019]
Alterations in embryonic neural stem cells play crucial roles in the pathogenesis of amyotrophic lateral sclerosis. We hypothesized that embryonic neural stem cells from SOD1(G93A) individuals might be more susceptible to oxidative injury, resulting in a propensity for neurodegeneration at later stages. In this study, embryonic neural stem cells obtained from human superoxide dismutase 1 mutant (SOD1(G93A)) and wild-type (SOD1(WT)) mouse models were exposed to H2O2. We assayed cell viability with mitochondrial succinic dehydrogenase colorimetric reagent, and measured cell apoptosis by flow cytometry. Moreover, we evaluated the expression of the adenosine monophosphate-activated protein kinase (AMPK) alpha-subunit, paired box 3 (Pax3) protein, and p53 in western blot analyses. Compared with SOD1(WT) cells, SOD1(G93A) embryonic neural stem cells were more likely to undergo H2O2-induced apoptosis. Phosphorylation of AMPK alpha in SOD1(G93A) cells was higher than that in SOD1(WT) cells. Pax3 expression was inversely correlated with the phosphorylation levels of AMPK alpha. p53 protein levels were also correlated with AMPKa phosphorylation levels. Compound C, an inhibitor of AMPK alpha, attenuated the effects of H2O2. These results suggest that embryonic neural stem cells from SOD1(G93A) mice are more susceptible to apoptosis in the presence of oxidative stress compared with those from wild-type controls, and the effects are mainly mediated by Pax3 and p53 in the AMPK alpha pathway.
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