DJ-1 Protein Inhibits Apoptosis in Cerebral Ischemia by Regulating the Notch1 and Nuclear Factor Erythroid2-Related Factor 2 Signaling Pathways

作者全名："Wang, Tingting; Xue, Ying; Li, Yumei; Gao, Sihao; Peng, Li; Zhao, Yong; Yu, Shanshan"

作者地址："[Wang, Tingting; Xue, Ying; Li, Yumei; Peng, Li; Zhao, Yong; Yu, Shanshan] Chongqing Med Univ, Coll Basic Med, Dept Pathol, Chongqing 400016, Peoples R China; [Wang, Tingting] Anhui Med Univ, Dept Pathol, Luan Hosp Affiliated, Anhui 237000, Peoples R China; [Xue, Ying; Li, Yumei; Peng, Li; Zhao, Yong; Yu, Shanshan] Chongqing Med Univ, Mol Med Diagnost & Testing Ctr, Chongqing 400016, Peoples R China; [Xue, Ying; Li, Yumei; Peng, Li; Zhao, Yong; Yu, Shanshan] Chongqing Med Univ, Dept Pathol, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Wang, Tingting] Luan Peoples Hosp, Dept Pathol, Anhui 237000, Peoples R China; [Gao, Sihao] Chongqing Med Univ, Childrens Hosp, Chongqing 400014, Peoples R China; [Yu, Shanshan] Chongqing Med Univ, Dept Pathol, Yixueyuan Rd 1, Chongqing 400016, Peoples R China"

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

来源：NEUROSCIENCE

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000872588400004

JCR分区：Q3

影响因子：3.3

年份：2022

卷号：504

期号：　

开始页：33

结束页：46

文献类型：Article

关键词：DJ-1; Notch1; Nrf2; DAPT; Apoptosis; Ischemia-reperfusion injury

摘要："DJ-1 plays a neuroprotective role in cerebral ischemia-reperfusion (I/R) injury and participates in the apoptosis of brain nerve cells, but the underlying mechanism is unclear. We explored the molecular pathways underlying this role using in vivo and in vitro approaches. Middle cerebral artery occlusion-reperfusion (MCAO/R) rat models and oxygen-glucose deprivation-reoxygenation (OGD/R) HAPI cell cultures were used to simulate cerebral ischemia-reperfusion injury. The interaction between DJ-1 and Notch1 was enhanced after MCAO/R in rats. After treatment of rats with DJ-1 siRNA, the expression of Notch1 and Nrf2 was down -regulated, and apoptosis was promoted. In contrast, the DJ-1 based peptide ND-13 upregulated the expression of Notch1 and Nrf2, and prevented apoptosis. In vitro, the Notch1 signaling pathway inhibitor DAPT reversed the neuroprotective effect of ND-13 and promoted apoptosis, weakened the interaction between DJ-1 and Notch1, and decreased the expression of proteins in the Notch1 and Nrf2 pathways. Thus, we found that DJ-1 inhibits apoptosis by regulating the Notch1 signaling pathway and Nrf2 expression in cerebral I/R injury. These results imply that DJ-1 is a potential therapeutic target for cerebral I/R injury.(c) 2022 IBRO. Published by Elsevier Ltd. All rights reserved."

基金机构：FUNDING - National Natural Science Foundation of Chongqing [cstc2020jcyj-msxmX0099]

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