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学科主题: 基础医学
题名:
Selective 14-3-3 gamma induction quenches p-beta-catenin Ser37/Bax-enhanced cell death in cerebral cortical neurons during ischemia
作者: Lai, X. J.1; Ye, S. Q.1; Zheng, L.1; Li, L.1; Liu, Q. R.1; Yu, S. B.1; Pang, Y.2,3; Jin, S.4; Li, Q.5; Yu, A. C. H.2,3; Chen, X. Q.1
关键词: 14-3-3 ; beta-catenin ; Bax ; neuron ; astrocyte ; stroke
刊名: CELL DEATH & DISEASE
发表日期: 2014-04-01
DOI: 10.1038/cddis.2014.152
卷: 5, 期:4
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cell Biology
研究领域[WOS]: Cell Biology
关键词[WOS]: TISSUE-PLASMINOGEN ACTIVATOR ; IN-VITRO ISCHEMIA ; CEREBROSPINAL-FLUID ; PROTEINS ; NEUROPROTECTION ; STROKE ; NEUROGLOBIN ; DISEASE ; 14-3-3-PROTEINS ; MECHANISMS
英文摘要:

Ischemia-induced cell death is a major cause of disability or death after stroke. Identifying the key intrinsic protective mechanisms induced by ischemia is critical for the development of effective stroke treatment. Here, we reported that 14-3-3 gamma was a selective ischemia-inducible survival factor in cerebral cortical neurons reducing cell death by downregulating Bax depend direct 14-3-3 gamma/p-beta-catenin Ser37 interactions in the nucleus. 14-3-3 gamma, but not other 14-3-3 isoforms, was upregulated in primary cerebral cortical neurons upon oxygen-glucose deprivation (OGD) as measured by quantitative PCR, western blot and fluorescent immunostaining. The selective induction of 14-3-3 gamma in cortical neurons by OGD was verified by the in vivo ischemic stroke model. Knocking down 14-3-3 gamma alone or inhibiting 14-3-3/client interactions was sufficient to induce cell death in normal cultured neurons and exacerbate OGD-induced neuronal death. Ectopic overexpression of 14-3-3 gamma significantly reduced OGD-induced cell death in cultured neurons. Co-immunoprecipitation and fluorescence resonance energy transfer demonstrated that endogenous 14-3-3 gamma bound directly to more p-beta-catenin Ser37 but not p-Bad, p-Ask-1, p-p53 and Bax. During OGD, p-beta-catenin Ser37 but not p-b-catenin Ser45 was increased prominently, which correlated with Bax elevation in cortical neurons. OGD promoted the entry of 14-3-3 gamma into the nuclei, in correlation with the increase of nuclear p-beta-catenin Ser37 in neurons. Overexpression of 14-3-3 gamma significantly reduced Bax expression, whereas knockdown of 14-3-3 gamma increased Bax in cortical neurons. Abolishing beta-catenin phosphorylation at Ser37 (S37A) significantly reduced Bax and cell death in neurons upon OGD. Finally, 14-3-3 gamma overexpression completely suppressed b-catenin-enhanced Bax and cell death in neurons upon OGD. Based on these data, we propose that the 14-3-3 gamma/p-beta-catenin Ser37/Bax axis determines cell survival or death of neurons during ischemia, providing novel therapeutic targets for ischemic stroke as well as other related neurological diseases.

语种: 英语
所属项目编号: 30470539 ; 30570555 ; 81070937 ; 81172397 ; 31070974 ; 31171009 ; 81271509 ; 2013ZHYX017 ; 7091004 ; 2011CB504400 ; 11PJ1401800
项目资助者: National Natural Science Foundation of China ; Fundamental Research Funds for the Central Universities, HUST ; Beijing Natural Science Foundation ; National Basic Research Program of China (973 Program) ; Shanghai Pujiang Program from Science and Technology Commission of Shanghai Municipality
WOS记录号: WOS:000335450400030
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/61114
Appears in Collections:基础医学院_神经生物学系_期刊论文

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作者单位: 1.Huazhong Univ Sci & Technol, Sch Basic Med, Dept Pathophysiol,Minist Educ, Hubei Prov Key Lab Neurol Dis,Key Lab Neurol Dis, Wuhan 430030, Peoples R China
2.Peking Univ, Sch Basic Med Sci, Neurosci Res Inst, Dept Neurobiol,Minist Educ, Beijing 100871, Peoples R China
3.Peking Univ, Minist Hlth PKU, Beijing 100871, Peoples R China
4.Huazhong Univ Sci & Technol, Sch Basic Med, Dept Pharmacol, Wuhan 430074, Peoples R China
5.Fudan Univ, Childrens Hosp, Translat Med Ctr Dev & Dis, Inst Pediat, Shanghai 200433, Peoples R China

Recommended Citation:
Lai, X. J.,Ye, S. Q.,Zheng, L.,et al. Selective 14-3-3 gamma induction quenches p-beta-catenin Ser37/Bax-enhanced cell death in cerebral cortical neurons during ischemia[J]. CELL DEATH & DISEASE,2014,5(4).
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