ZNRF2 attenuates focal cerebral ischemia/reperfusion injury in rats by inhibiting mTORC1-mediated autophagy

作者全名："Gu, Chao; Yang, Junqing; Luo, Ying; Ran, Dongzhi; Tan, Xiaodan; Xiang, Pu; Fei, Huizhi; Lu, Yi; Guo, Wenjia; Tu, Yujun; Liu, Xia; Wang, Hong"

作者地址："[Gu, Chao; Yang, Junqing; Luo, Ying; Ran, Dongzhi; Tan, Xiaodan; Xiang, Pu; Fei, Huizhi; Lu, Yi; Guo, Wenjia; Tu, Yujun; Liu, Xia; Wang, Hong] Chongqing Med Univ, Dept Pharmacol, Key Lab Biochem & Mol Pharmacol, Chongqing 400016, Peoples R China; [Xiang, Pu] Dianjiang Peoples Hosp Chongqing, Chongqing 408300, Peoples R China"

通信作者："Wang, H (corresponding author), Chongqing Med Univ, Dept Pharmacol, 1 Med Coll Rd, Chongqing, Peoples R China."

来源：EXPERIMENTAL NEUROLOGY

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000658257300003

JCR分区：Q1

影响因子：5.3

年份：2021

卷号：342

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：CIRI; ZNRF2; mTOR; Autophagy; Primary neurons; OGD; R

摘要："Zinc and ring finger 2 (ZNRF2), an E3 ubiquitin ligase, plays a crucial role in many diseases. However, its role in cerebral ischemia/reperfusion injury (CIRI) still remains unknown. In this study, the function and molecular mechanism of ZNRF2 in CIRI in vivo and vitro was studied. ZNRF2 was found to be dramatically downregulated in CIRI. Overexpression of ZNRF2 could significantly reduce the neurological deficit, brain infarct volume and histopathological damage of cortex in middle cerebral artery occlusion/reperfusion. Concomitantly, overexpression of ZNRF2 increased the primary neuronal viability and decreased the neuronal apoptosis induced by oxygen-glucose deprivation and reoxygenation (OGD/R). Mechanistically, overexpression of ZNRF2 inhibited the over-induction of autophagy induced by OGD/R which was abolished by mTORC1 inhibitor rapamycin. It can be concluded that ZNRF2 plays a protective effect in CIRI and the underlying mechanism may be related to the inhibition of mTORC1-mediated autophagy."

基金机构：Chinese Postdoctoral Science FoundationChina Postdoctoral Science Foundation [2019M663451]

基金资助正文：Acknowledgement is given to the "Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology" for providing an experimental platform and Dianjiang People's Hospital of Chongqing for clinical samples. The study was approved by the fellowship Chinese Postdoctoral Science Foundation (2019M663451) .