Cerebral ischemia-reperfusion-induced autophagy protects against neuronal injury by mitochondrial clearance

doi:10.4161/auto.25132

科研成果详情

题名	Cerebral ischemia-reperfusion-induced autophagy protects against neuronal injury by mitochondrial clearance
作者	Zhang, Xiangnan 1; Yan, Haijing 1; Yuan, Yang 1; Gao, Jieqiong2; Shen, Zhe 1; Cheng, Yun 1; Shen, Yao2; Wang, Rong-Rong 1; Wang, Xiaofen2; Hu, Wei-Wei 1; Wang, Guanghui 3; Chen, Zhong 1
发表期刊	AUTOPHAGY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	cerebral ischemia autophagy neuroprotection mitochondria mitophagy
其他关键词	OXIDATIVE STRESS ; CYTOCHROME-C ; CELL-DEATH ; RAT MODEL ; IN-VITRO ; ACTIVATION ; NEUROPROTECTION ; INDUCTION ; MITOPHAGY ; HYPOXIA
摘要	Cerebral ischemia-reperfusion (I-R) is a complex pathological process. Although autophagy can be evoked by ischemia, its involvement in the reperfusion phase after ischemia and its contribution to the fate of neurons remains largely unknown. In the present investigation, we found that autophagy was activated in the reperfusion phase, as revealed in both mice with middle cerebral artery occlusion and oxygen-glucose deprived cortical neurons in culture. Interestingly, in contrast to that in permanent ischemia, inhibition of autophagy (by 3-methyladenine, bafilomycin A(1), Atg7 knockdown or in atg5(-/-) MEF cells) in the reperfusion phase reinforced, rather than reduced, the brain and cell injury induced by I-R. Inhibition of autophagy either with 3-methyladenine or Atg7 knockdown enhanced the I-R-induced release of cytochrome c and the downstream activation of apoptosis. Moreover, MitoTracker Red-labeled neuronal mitochondria increasingly overlapped with GFP-LC3-labeled autophagosomes during reperfusion, suggesting the presence of mitophagy. The mitochondrial clearance in I-R was reversed by 3-methyladenine and Atg7 silencing, further suggesting that mitophagy underlies the neuroprotection by autophagy. In support, administration of the mitophagy inhibitor mdivi-1 in the reperfusion phase aggravated the ischemia-induced neuronal injury both in vivo and in vitro. PARK2 translocated to mitochondria during reperfusion and Park2 knockdown aggravated ischemia-induced neuronal cell death. In conclusion, the results indicated that autophagy plays different roles in cerebral ischemia and subsequent reperfusion. The protective role of autophagy during reperfusion may be attributable to mitophagy-related mitochondrial clearance and inhibition of downstream apoptosis. PARK2 may be involved in the mitophagy process.
资助项目	National Basic Research of China 973 ProgramNational Basic Research Program of China [2011CB504403]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81030061, 81273506, 81173040, 81102429, 81221003]; China Postdoctoral Science FoundationChina Postdoctoral Science Foundation [2011M501022]
出版者	TAYLOR & FRANCIS INC
出版地	PHILADELPHIA
ISSN	1554-8627
EISSN	1554-8635
卷号	9 期号:9 页码:1321-1333
DOI	10.4161/auto.25132
WOS类目	Cell Biology
WOS研究方向	Cell Biology
WOS记录号	WOS:000327579500006
收录类别	SCIE ; SCOPUS
发表日期	2013-09-01
URL	查看原文
Scopus记录号	2-s2.0-84884306536
自科自定义期刊分类	T3(B)类
引用统计	被引频次：341[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/6481
专题	检验医学院（生命科学学院、生物学实验教学中心）
通讯作者	Chen, Zhong
作者单位	1.Zhejiang Univ, Coll Pharmaceut Sci, Dept Pharmacol,Zhejiang Prov Key Lab Neurobiol, Key Lab Med Neurobiol,Minist Hlth China, Hangzhou 310003, Zhejiang, Peoples R China; 2.Wenzhou Med Coll, Sch Life Sci, Zhejiang Prov Key Lab Med Genet, Wenzhou, Peoples R China; 3.Soochow Univ, Coll Pharmaceut Sci, Dept Pharmacol, Lab Mol Neuropathol, Suzhou, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Xiangnan,Yan, Haijing,Yuan, Yang,et al. Cerebral ischemia-reperfusion-induced autophagy protects against neuronal injury by mitochondrial clearance[J]. AUTOPHAGY,2013,9(9):1321-1333.
APA	Zhang, Xiangnan., Yan, Haijing., Yuan, Yang., Gao, Jieqiong., Shen, Zhe., ... & Chen, Zhong. (2013). Cerebral ischemia-reperfusion-induced autophagy protects against neuronal injury by mitochondrial clearance. AUTOPHAGY, 9(9), 1321-1333.
MLA	Zhang, Xiangnan,et al."Cerebral ischemia-reperfusion-induced autophagy protects against neuronal injury by mitochondrial clearance".AUTOPHAGY 9.9(2013):1321-1333.