DJ-1 activates the Atg5-Atg12-Atg16L1 complex via Sirt1 to influence microglial polarization and alleviate cerebral ischemia/ reperfusion-induced inflammatory injury

作者全名："Zhao, Na; Li, Yumei; Wang, Chenglong; Xue, Ying; Peng, Li; Wang, Tingting; Zhao, Yong; Xu, Ge; Yu, Shanshan"

作者地址："[Zhao, Na; Li, Yumei; Wang, Chenglong; Xue, Ying; Peng, Li; Wang, Tingting; Zhao, Yong; Yu, Shanshan] Chongqing Med Univ, Coll Basic Med, Dept Pathol, Chongqing 400016, Peoples R China; [Zhao, Na] Chengdu Second Peoples Hosp, Chengdu 610000, Peoples R China; [Wang, Chenglong] Chongqing Hosp Tradit Chinese Med, Dept Pathol, Chongqing 400021, Peoples R China; [Xu, Ge] Chongqing Med Univ, Inst Life Sci, Chongqing 400016, Peoples R China; [Yu, Shanshan] Chongqing Med Univ, Coll Basic Med, Dept Pathol, Yixueyuan Rd 1, Chongqing 400016, Peoples R China"

通信作者："Yu, SS (通讯作者)，Chongqing Med Univ, Coll Basic Med, Dept Pathol, Chongqing 400016, Peoples R China.; Yu, SS (通讯作者)，Chongqing Med Univ, Coll Basic Med, Dept Pathol, Yixueyuan Rd 1, Chongqing 400016, Peoples R China."

来源：NEUROCHEMISTRY INTERNATIONAL

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000800013200004

JCR分区：Q2

影响因子：4.2

年份：2022

卷号：157

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：DJ-1; Microglial polarization; Sirt1; Autophagy; Cerebral I; R injury

摘要："Background: After cerebral ischemia/reperfusion (I/R) injury, activated microglia can be polarized towards different phenotypes (the proinflammatory M1 phenotype or the anti-inflammatory M2 phenotype) to regulate neuroinflammation. Our previous research showed that DJ-1 has anti-inflammatory effects in cerebral I/R. Here, we examined whether the neuroprotective effect of DJ-1 is related to the autophagy-associated Atg5-Atg12Atg161L1 complex and whether Sirt1 is involved in the influence of DJ-1 by mediating microglial polarization and ameliorating cerebral I/R injury. Methods: To answer these questions, we adopted the middle cerebral artery occlusion/reperfusion (MCAO/R) model to simulate I/R injury, knocked down the expression of DJ-1 with siRNA, and used the chemical inhibitor EX-527 to inhibit the expression of Sirt1. Related indexes were evaluated by Western blotting, immunoprecipitation and transmission electron microscopy. Results: Interference with DJ-1 promotes the polarization of microglia from the anti-inflammatory phenotype to the proinflammatory phenotype. Addition of a Sirt1 inhibitor following DJ-1 interference enhances the effect of DJ-1 interference on microglial polarization, decreases the level of the Atg5-Atg12-Atg16L1 complex, and inhibits autophagy. Conclusion: These results suggest that DJ-1 regulates the polarization of microglia during cerebral I/R injury, possibly by activating the Atg5-Atg12-Atg16L1 complex through Sirt1 to promote autophagy."

基金机构：National Natural Science Foundation of Chongqing - National Nat-ural Science Youth Foundation of China [82101376]

基金资助正文：Acknowledgements The National Natural Science Foundation of Chongqing (No.cstc2020jcyj-msxmX0099) . The study was funded by the National Nat-ural Science Youth Foundation of China (No.82101376) .