c-Abl-p38 alpha signaling plays an important role in MPTP-induced neuronal death

doi:10.1038/cdd.2015.135

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	c-Abl-p38 alpha signaling plays an important role in MPTP-induced neuronal death
	Wu, R.1,2; Chen, H.1,3; Ma, J.1,2; He, Q.1,2; Huang, Q.4,5; Liu, Q.6; Li, M.4,5; Yuan, Z.1,2,3
	2016-03-01
发表期刊	CELL DEATH AND DIFFERENTIATION
摘要	Oxidative stress is a major cause of sporadic Parkinson's disease (PD). Here, we demonstrated that c-Abl plays an important role in oxidative stress-induced neuronal cell death. C-Abl, a nonreceptor tyrosine kinase, was activated in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-induced acute PD model. Conditional knockout of c-Abl in neurons or treatment of mice with STI571, a c-Abl family kinase inhibitor, reduced the loss of dopaminergic neurons and ameliorated the locomotive defects induced by short-term MPTP treatment. By combining the SILAC (stable isotope labeling with amino acids in cell culture) technique with other biochemical methods, we identified p38 alpha as a major substrate of c-Abl both in vitro and in vivo and c-Abl-mediated phosphorylation is critical for the dimerization of p38 alpha. Furthermore, p38 alpha inhibition mitigated the MPTP-induced loss of dopaminergic neurons. Taken together, these data suggested that c-Abl-p38 alpha signaling may represent a therapeutic target for PD.
文章类型	Article
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
DOI	10.1038/cdd.2015.135
关键词[WOS]	ABL TYROSINE KINASE ; C-ABL ; PARKINSONS-DISEASE ; PHOSPHORYLATION ; ACTIVATION ; PATHWAY ; ALPHA ; MODEL ; PATHOGENESIS ; DEGRADATION
收录类别	SCI
语种	英语
项目资助者	National Science Foundation of China(81125010 ; National Science Foundation of China(81125010 ; National Science Foundation of China(81125010 ; National Science Foundation of China(81125010 ; National Basic Research Program of China(973-2011CB504105 ; National Basic Research Program of China(973-2011CB504105 ; National Basic Research Program of China(973-2011CB504105 ; National Basic Research Program of China(973-2011CB504105 ; Cross-disciplinary Collaborative Teams Program for Science, Technology and Innovation from Chinese Academy of Sciences ; Cross-disciplinary Collaborative Teams Program for Science, Technology and Innovation from Chinese Academy of Sciences ; Cross-disciplinary Collaborative Teams Program for Science, Technology and Innovation from Chinese Academy of Sciences ; Cross-disciplinary Collaborative Teams Program for Science, Technology and Innovation from Chinese Academy of Sciences ; 81030025) ; 81030025) ; 81030025) ; 81030025) ; 973-2012CB910701 ; 973-2012CB910701 ; 973-2012CB910701 ; 973-2012CB910701 ; 2013DFA31990) ; 2013DFA31990) ; 2013DFA31990) ; 2013DFA31990)
WOS研究方向	Biochemistry & Molecular Biology ; Cell Biology
WOS类目	Biochemistry & Molecular Biology ; Cell Biology
WOS记录号	WOS:000369726800015
引用统计	被引频次：53[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.hfcas.ac.cn:8080/handle/334002/22283
专题	中科院强磁场科学中心
作者单位	1.Chinese Acad Sci, Inst Biophys, State Key Lab Brain & Cognit Sci, Beijing 100101, Peoples R China 2.Univ Chinese Acad Sci, Coll Life Sci, Beijing 100049, Peoples R China 3.Beijing Inst Brain Disorders, Ctr Alzheimers Dis, Beijing 100069, Peoples R China 4.Sun Yat Sen Univ, Zhongshan Sch Med, Dept Pharmacol, Guangzhou 510080, Guangdong, Peoples R China 5.Sun Yat Sen Univ, Zhongshan Sch Med, Prote Ctr, Guangzhou 510080, Guangdong, Peoples R China 6.Chinese Acad Sci, High Magnet Field Lab, Hefei 230031, Anhui, Peoples R China
推荐引用方式 GB/T 7714	Wu, R.,Chen, H.,Ma, J.,et al. c-Abl-p38 alpha signaling plays an important role in MPTP-induced neuronal death[J]. CELL DEATH AND DIFFERENTIATION,2016,23(2):542-552.
APA	Wu, R..,Chen, H..,Ma, J..,He, Q..,Huang, Q..,...&Yuan, Z..(2016).c-Abl-p38 alpha signaling plays an important role in MPTP-induced neuronal death.CELL DEATH AND DIFFERENTIATION,23(2),542-552.
MLA	Wu, R.,et al."c-Abl-p38 alpha signaling plays an important role in MPTP-induced neuronal death".CELL DEATH AND DIFFERENTIATION 23.2(2016):542-552.

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