{
    "abstract": "Cerebral ischemia-reperfusion injury (CIRI) exacerbates post-stroke brain damage. We aimed to understand the role of glucose-6-phosphate dehydrogenase (G6PD) in CIRI and mitophagy.\nLentivirus and small interfering RNA were utilized to suppress G6PD in tissues and cells, leading to the establishment of in vivo and in vitro models of ischemia-reperfusion following middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation/ reoxygenation (OGD/R). The expression and function of G6PD were investigated through differential gene analysis and weighted correlation network analysis (WGCNA), immunofluorescence, and western blotting (WB).\nG6PD mRNA levels increased 3 d after MCAO, and G6PD protein expression was elevated in the ischemic penumbra of mice and HT22 cells following OGD/R. G6PD knockdown increased neural deficits, enlarged infarct volume in mice after CIRI, and reduced HT22 cell survival during OGD/R. WGCNA indicated a correlation between G6PD and mitophagy in CIRI. Following G6PD knockdown, the p-DRP1/DRP ratio increased, the PINK1/Parkin pathway was further activated, and TOMM20 expression was downregulated. The mitophagy inhibitor Mdivi-1 reversed these changes, as well as the nerve damage caused by G6PD knockdown, and alleviated mitochondrial damage in the ischemic penumbra.\nThe role of G6PD in CIRI was revealed and its interaction with mitophagy was explored, providing important insights for understanding the molecular mechanism of CIRI and developing new therapeutic strategies.",
    "authors": [
        {
            "affiliation": "Central Laboratory, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China; Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China.",
            "firstname": "Yina",
            "initials": "Y",
            "lastname": "Li"
        },
        {
            "affiliation": "Central Laboratory, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China; Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China.",
            "firstname": "Yikun",
            "initials": "Y",
            "lastname": "Gao"
        },
        {
            "affiliation": "Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China.",
            "firstname": "Guixiang",
            "initials": "G",
            "lastname": "Yu"
        },
        {
            "affiliation": "Central Laboratory, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China; Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China.",
            "firstname": "Yingze",
            "initials": "Y",
            "lastname": "Ye"
        },
        {
            "affiliation": "Central Laboratory, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China; Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China.",
            "firstname": "Hua",
            "initials": "H",
            "lastname": "Zhu"
        },
        {
            "affiliation": "Central Laboratory, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China; Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China.",
            "firstname": "Jin",
            "initials": "J",
            "lastname": "Wang"
        },
        {
            "affiliation": "Central Laboratory, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China; Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China.",
            "firstname": "Yilin",
            "initials": "Y",
            "lastname": "Li"
        },
        {
            "affiliation": "Cancer Center, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China. Electronic address: chenleiwhu@whu.edu.cn.",
            "firstname": "Lei",
            "initials": "L",
            "lastname": "Chen"
        },
        {
            "affiliation": "Central Laboratory, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China; Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China. Electronic address: gulijuan@whu.edu.cn.",
            "firstname": "Lijuan",
            "initials": "L",
            "lastname": "Gu"
        }
    ],
    "conclusions": null,
    "copyrights": "Copyright \u00a9 2024. Published by Elsevier Inc.",
    "doi": "10.1016/j.lfs.2024.123367",
    "journal": "Life sciences",
    "keywords": [
        "Cerebral ischemia-reperfusion injury",
        "G6PD",
        "Mitophagy",
        "Neurological dysfunction",
        "PINK1/Parkin pathway"
    ],
    "methods": null,
    "publication_date": "2025-01-06",
    "pubmed_id": "39756510",
    "results": null,
    "title": "G6PD protects against cerebral ischemia-reperfusion injury by inhibiting excessive mitophagy.",
    "xml": "<Element 'PubmedArticle' at 0x788506544a40>"
}