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学科主题: 临床医学
题名:
Adenosine monophosphate-activated protein kinase activation enhances embryonic neural stem cell apoptosis in a mouse model of amyotrophic lateral sclerosis
作者: Sui, Yanling; Zhao, Zichun; Liu, Rong; Cal, Bin; Fan, Dongsheng
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
刊名: NEURAL REGENERATION RESEARCH
发表日期: 2014-10-01
DOI: 10.4103/1673-5374.143421
卷: 9, 期:19, 页:1770-1778
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cell Biology ; Neurosciences
研究领域[WOS]: Cell Biology ; Neurosciences & Neurology
关键词[WOS]: 2-HIT HYPOTHESIS ; PROGENITOR CELLS ; DISEASE ; ENERGY ; MICE ; PROLIFERATION ; DEGENERATION ; NEUROGENESIS ; METABOLISM ; MUTANT
英文摘要:

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.

语种: 英语
所属项目编号: 81030019
项目资助者: National Natural Sciences Foundation of China
WOS记录号: WOS:000344637100010
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57920
Appears in Collections:北京大学第三临床医学院_神经内科_期刊论文

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作者单位: Peking Univ, Hosp 3, Dept Neurol, Beijing 100191, Peoples R China

Recommended Citation:
Sui, Yanling,Zhao, Zichun,Liu, Rong,et al. Adenosine monophosphate-activated protein kinase activation enhances embryonic neural stem cell apoptosis in a mouse model of amyotrophic lateral sclerosis[J]. NEURAL REGENERATION RESEARCH,2014,9(19):1770-1778.
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