DJ-1 inhibits ferroptosis in cerebral ischemia-reperfusion via ATF4/ HSPA5 pathway

作者全名："Li, Yumei; Chen, Tianyi; Xue, Ying; Wang, Yuan; Peng, Li; Wang, Chenglong; Yu, Shanshan"

作者地址："[Li, Yumei; Chen, Tianyi; Xue, Ying; Wang, Yuan; Peng, Li; Wang, Chenglong; Yu, Shanshan] Chongqing Med Univ, Coll Basic Med, Dept Pathol, Chongqing 400016, Peoples R China; [Li, Yumei] Chengdu Womens & Childrens Cent Hosp, Dept Pathol, Chengdu 610000, Peoples R China; [Chen, Tianyi; Xue, Ying; Wang, Yuan; Peng, Li; Yu, Shanshan] Chongqing Med Univ, Mol Med Diagnost & Testing Ctr, Chongqing 400016, Peoples R China; [Chen, Tianyi; Xue, Ying; Wang, Yuan; Peng, Li; Yu, Shanshan] Chongqing Med Univ, Affiliated Hosp 1, Dept Pathol, Chongqing 400016, Peoples R China; [Wang, Chenglong] Chongqing Hosp Tradit Chinese Med, Dept Pathol, Chongqing 400021, 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, Mol Med Diagnost & Testing Ctr, Chongqing 400016, Peoples R China.; Yu, SS (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Pathol, Chongqing 400016, Peoples R China.; Yu, SS (通讯作者)，Chongqing Med Univ, Dept Pathol, Yixueyuan Rd 1, Chongqing 400016, Peoples R China."

来源：NEUROCHEMISTRY INTERNATIONAL

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:001099247500001

JCR分区：Q1

影响因子：4.4

年份：2023

卷号：171

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：DJ-1; ND-13; Ferroptosis; Mitochondria; Cerebral ischemia-reperfusion injury

摘要："DJ-1 has been confirmed to have neuroprotective effects. Ferroptosis is an iron-dependent programmed cell death mode associated with ischemic stroke. The ATF4/HSPA5 pathway has been shown to play an important role in the regulation of ferroptosis. To explore the role and possible mechanism of DJ-1 in regulating ferroptosis in cerebral ischemia-reperfusion injury. In this study, Middle cerebral artery occlusion/reperfusion (MCAO/R) was used to simulate cerebral ischemia-reperfusion injury in vivo. Detected ferroptosis-related indicators and observed mitochondrial morphology in brain tissue using transmission electron microscopy. ATF4 was subsequently interfered to observe the effect of DJ-1 on ferroptosis. The results suggest that after interfering with DJ-1, the iron content and malondialdehyde (MDA) content of ferroptosis-related indicators increased, the GSH content decreased, and the mitochondrial structure was severely damaged. We then found that DJ-1 attenuated ferroptosis following ATF4 reduction. In this study, we found that the neuroprotective effect of DJ-1 is related to the inhibition of ferroptosis, and its molecular mechanism is closely related to the ATF4/HSPA5 pathway, which may play a key role in inhibiting brain ischemia-reperfusion (I/R) ferroptosis."

基金机构：Intelligent Medicine Research Project of Chongqing Medical University [ZHYX202210]; National Natural Science Foundation of Chongqing [cstc2020jcyj-msxmX0099]

基金资助正文：This research was funded by the Intelligent Medicine Research Project of Chongqing Medical University (No.ZHYX202210) and the National Natural Science Foundation of Chongqing (No. cstc2020jcyj-msxmX0099).