Upregulation of CDGSH iron sulfur domain 2 attenuates cerebral ischemia/reperfusion injury
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 stud...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2023-01-01
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| Series: | Neural Regeneration Research |
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| Online Access: | http://www.nrronline.org/article.asp?issn=1673-5374;year=2023;volume=18;issue=7;spage=1512;epage=1520;aulast=Hu |
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| author | Miao Hu Jie Huang Lei Chen Xiao-Rong Sun Zi-Meng Yao Xu-Hui Tong Wen-Jing Jin Yu-Xin Zhang Shu-Ying Dong |
| author_facet | Miao Hu Jie Huang Lei Chen Xiao-Rong Sun Zi-Meng Yao Xu-Hui Tong Wen-Jing Jin Yu-Xin Zhang Shu-Ying Dong |
| author_sort | Miao Hu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T23:23:40Z |
| format | Article |
| id | doaj.art-fa4b797ffb5143fcb9c9283ad752a800 |
| institution | Directory Open Access Journal |
| issn | 1673-5374 |
| language | English |
| last_indexed | 2024-04-10T23:23:40Z |
| publishDate | 2023-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Neural Regeneration Research |
| spelling | doaj.art-fa4b797ffb5143fcb9c9283ad752a8002023-01-12T13:29:30ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53742023-01-011871512152010.4103/1673-5374.355766Upregulation of CDGSH iron sulfur domain 2 attenuates cerebral ischemia/reperfusion injuryMiao HuJie HuangLei ChenXiao-Rong SunZi-Meng YaoXu-Hui TongWen-Jing JinYu-Xin ZhangShu-Ying DongCDGSH 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.http://www.nrronline.org/article.asp?issn=1673-5374;year=2023;volume=18;issue=7;spage=1512;epage=1520;aulast=Hucerebral 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 |
| spellingShingle | Miao Hu Jie Huang Lei Chen Xiao-Rong Sun Zi-Meng Yao Xu-Hui Tong Wen-Jing Jin Yu-Xin Zhang Shu-Ying Dong Upregulation of CDGSH iron sulfur domain 2 attenuates cerebral ischemia/reperfusion injury Neural Regeneration Research 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 |
| title | Upregulation of CDGSH iron sulfur domain 2 attenuates cerebral ischemia/reperfusion injury |
| title_full | Upregulation of CDGSH iron sulfur domain 2 attenuates cerebral ischemia/reperfusion injury |
| title_fullStr | Upregulation of CDGSH iron sulfur domain 2 attenuates cerebral ischemia/reperfusion injury |
| title_full_unstemmed | Upregulation of CDGSH iron sulfur domain 2 attenuates cerebral ischemia/reperfusion injury |
| title_short | Upregulation of CDGSH iron sulfur domain 2 attenuates cerebral ischemia/reperfusion injury |
| title_sort | upregulation of cdgsh iron sulfur domain 2 attenuates cerebral ischemia reperfusion injury |
| topic | 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 |
| url | http://www.nrronline.org/article.asp?issn=1673-5374;year=2023;volume=18;issue=7;spage=1512;epage=1520;aulast=Hu |
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