title: Adenosine monophosphate-activated protein kinase activation enhances embryonic neural stem cell apoptosis in a mouse model of amyotrophic lateral sclerosis.
abstract: 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) α-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 AMPKα in SOD1(G93A) cells was higher than that in SOD1(WT) cells. Pax3 expression was inversely correlated with the phosphorylation levels of AMPKα. p53 protein levels were also correlated with AMPKα phosphorylation levels. Compound C, an inhibitor of AMPKα, 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 AMPKα pathway.
authors.affiliation: Department of Neurology, Peking University Third Hospital, Beijing, China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Sui
authors.affiliation: Department of Neurology, Peking University Third Hospital, Beijing, China.
authors.forename: Zichun
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Peking University Third Hospital, Beijing, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Neurology, Peking University Third Hospital, Beijing, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Cai
authors.affiliation: Department of Neurology, Peking University Third Hospital, Beijing, China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Fan
keywords: NSFC grants; SOD1G93A mouse; adenosine monophosphate-activated protein kinase α; amyotrophic lateral sclerosis; apoptosis; embryonic neural stem cells; hydrogen peroxide; nerve regeneration; neural regeneration; neuroderegeneration; oxidative stress; p53; paired box 3