Upregulation of CDGSH iron sulfur domain 2 attenuates cerebral ischemia/reperfusion injury

作     者：Miao Hu Jie Huang Lei Chen Xiao-Rong Sun Zi-Meng Yao Xu-Hui Tong Wen-Jing Jin Yu-Xin Zhang Shu-Ying Dong Miao Hu;Jie Huang;Lei Chen;Xiao-Rong Sun;Zi-Meng Yao;Xu-Hui Tong;Wen-Jing Jin;Yu-Xin Zhang;Shu-Ying Dong

作者机构：Department of PharmacologySchool of PharmacyBengbu Medical CollegeBengbuAnhui ProvinceChina Key Laboratory of Cardiovascular and Cerebrovascular DiseasesBengbu Medical CollegeBengbuAnhui ProvinceChina Anhui Engineering Technology Research Center of Biochemical PharmaceuticalBengbuAnhui ProvinceChina 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2023年第18卷第7期

页      面：1512-1520页

核心收录：

学科分类：0710[理学-生物学] 1006[医学-中西医结合] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 100602[医学-中西医结合临床] 

基　　金：supported by the National Natural Science Foundation of China,No.81402930 Natural Science Foundation of Universities in Anhui Province,No.KJ2021A0688 National College Students Innovation and Entrepreneurship Program,No.202110367071 Key projects of science and technology projects of Bengbu Medical College,No.2020byzd017 512 Talents Training Program of Bengbu Medical College,No.BY51201104(all to SYD). 

主　　题：cerebral ischemia/reperfusion injury CDGSH iron sulfur domain 2 ferroptosis glutathione peroxidase 4 heme oxygenase 1 HT22 nuclear-factor E2-related factor 2 oxygen-glucose deprivation/reoxygenation injury stroke transferrin receptor 1 

摘      要：CDGSH iron sulfur domain 2 can inhibit ferroptosis,which has been associated with cerebral ischemia/reperfusion,in individuals with head and neck cancer.Therefore,CDGSH iron sulfur domain 2 may be implicated in cerebral ischemia/reperfusion injury.To validate this hypothesis in the present study,we established mouse models of occlusion of the middle cerebral artery and HT22 cell models of oxygen-glucose deprivation and reoxygenation to mimic cerebral ischemia/reperfusion injury in vivo and in vitro,respectively.We found remarkably decreased CDGSH iron sulfur domain 2 expression in the mouse brain tissue and HT22 cells.When we used adeno-associated virus and plasmid to up-regulate CDGSH iron sulfur domain 2 expression in the brain tissue and HT22 cell models separately,mouse neurological dysfunction was greatly improved;the cerebral infarct volume was reduced;the survival rate of HT22 cells was increased;HT22 cell injury was alleviated;the expression of ferroptosis-related glutathione peroxidase 4,cystine-glutamate antiporter,and glutathione was increased;the levels of malondialdehyde,iron ions,and the expression of transferrin receptor 1 were decreased;and the expression of nuclear-factor E2-related factor 2/heme oxygenase 1 was increased.Inhibition of CDGSH iron sulfur domain 2 upregulation via the nuclear-factor E2-related factor 2 inhibitor ML385 in oxygen-glucose deprived and reoxygenated HT22 cells blocked the neuroprotective effects of CDGSH iron sulfur domain 2 up-regulation and the activation of the nuclear-factor E2-related factor 2/heme oxygenase 1 pathway.Our data indicate that the up-regulation of CDGSH iron sulfur domain 2 can attenuate cerebral ischemia/reperfusion injury,thus providing theoretical support from the perspectives of cytology and experimental zoology for the use of this protein as a therapeutic target in patients with cerebral ischemia/reperfusion injury.