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 

机构地区：[1]Department of Pharmacology,School of Pharmacy,Bengbu Medical College,Bengbu,Anhui Province,China [2]Key Laboratory of Cardiovascular and Cerebrovascular Diseases,Bengbu Medical College,Bengbu,Anhui Province,China [3]Anhui Engineering Technology Research Center of Biochemical Pharmaceutical,Bengbu,Anhui Province,China

出　　处：《Neural Regeneration Research》2023年第7期1512-1520,共9页中国神经再生研究（英文版）

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).

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.

关 键 词：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 

分 类 号：R965[医药卫生—药理学]