ARRB1/beta-arrestin-1 mediates neuroprotection through coordination of BECN1-dependent autophagy in cerebral ischemia
文献类型：期刊论文
| 作者 | Wang, P; Xu, TY; Wei, K; Guan, YF; Wang, X; Xu, H; Su, DF; Pei, G; Miao, CY |
| 刊名 | AUTOPHAGY
 |
| 出版日期 | 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 |
| 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. |
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