ARRB1/beta-arrestin-1 mediates neuroprotection through coordination of BECN1-dependent autophagy in cerebral ischemia

	ARRB1/beta-arrestin-1 mediates neuroprotection through coordination of BECN1-dependent autophagy in cerebral ischemia
	Wang, P; Xu, TY; Wei, K; Guan, YF; Wang, X; Xu, H; Su, DF; Pei, G; Miao, CY
刊名	AUTOPHAGY
	2014
卷号	10 期号:9 页码:1535-1548
关键词	ARRB1 autophagy cerebral ischemia BECN1 neuron
通讯作者	Pei, G (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai, Peoples R China.,gpei@sibs.ac.cn
英文摘要	Autophagy, a highly conserved process conferring cytoprotection against stress, contributes to the progression of cerebral ischemia. beta-arrestins are multifunctional proteins that mediate receptor desensitization and serve as important signaling scaffolds involved in numerous physiopathological processes. Here, we show that both ARRB1 (arrestin, beta 1) and ARRB2 (arrestin, beta 2) were upregulated by cerebral ischemic stress. Knockout of Arrb1, but not Arrb2, aggravated the mortality, brain infarction, and neurological deficit in a mouse model of cerebral ischemia. Accordingly, Arrb1-deficient neurons exhibited enhanced cell injury upon oxygen-glucose deprivation (OGD), an in vitro model of ischemia. Deletion of Arrb1 did not affect the cerebral ischemia-induced inflammation, oxidative stress, and nicotinamide phosphoribosyltransferase upregulation, but markedly suppressed autophagy and induced neuronal apoptosis/necrosis in vivo and in vitro. Additionally, we found that ARRB1 interacted with BECN1/Beclin 1 and PIK3C3/Vps34, 2 major components of the BECN1 autophagic core complex, under the OGD condition but not normal conditions in neurons. Finally, deletion of Arrb1 impaired the interaction between BECN1 and PIK3C3, which is a critical event for autophagosome formation upon ischemic stress, and markedly reduced the kinase activity of PIK3C3. These findings reveal a neuroprotective role for ARRB1, in the context of cerebral ischemia, centered on the regulation of BECN1-dependent autophagosome formation.
学科主题	Cell Biology
类目[WOS]	Cell Biology
关键词[WOS]	BREAST-CANCER CELLS ; BETA-ARRESTIN ; NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE ; ISCHEMIA/REPERFUSION INJURY ; REGULATES AUTOPHAGY ; GENE-TRANSCRIPTION ; REPERFUSION INJURY ; ARTERY OCCLUSION ; NEURONAL INJURY ; PROTEIN-KINASE
收录类别	SCI
语种	英语
WOS记录号	WOS:000341647200006
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/224]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Wang, P,Xu, TY,Wei, K,et al. ARRB1/beta-arrestin-1 mediates neuroprotection through coordination of BECN1-dependent autophagy in cerebral ischemia[J]. AUTOPHAGY,2014,10(9):1535-1548.
APA	Wang, P.,Xu, TY.,Wei, K.,Guan, YF.,Wang, X.,...&Miao, CY.(2014).ARRB1/beta-arrestin-1 mediates neuroprotection through coordination of BECN1-dependent autophagy in cerebral ischemia.AUTOPHAGY,10(9),1535-1548.
MLA	Wang, P,et al."ARRB1/beta-arrestin-1 mediates neuroprotection through coordination of BECN1-dependent autophagy in cerebral ischemia".AUTOPHAGY 10.9(2014):1535-1548.