{"title":"FTO-mediated m6A modification of FTH1 inhibits ferroptosis of neurons in neonatal cerebral hypoxic ischaemia","authors":"Yanhong Chen, Jia Huang","doi":"10.1615/critreveukaryotgeneexpr.2024054011","DOIUrl":null,"url":null,"abstract":"FTO is aberrantly expressed in brain disorders. However, the roles of FTO in neonatal hypoxic-ischemic brain injury (HIE) are still unclear. This study aims to investigate the potential of FTO in neonatal HIE. Oxygen-glucose deprivation (OGD) was used to establish HIE in vitro. mRNA levels were detected by RT-qPCR. Protein expression was detected by western blot. The levels of MDA, SOD, Fe2+ and GSH was detected by specific kit. m6A sites were analyzed using SRAMP and further verify by MeRIP assay. Cell proliferation was determined by CCK-8. Cell death was determined by PI staining. FTO was downregulated in patients with neonatal HIE and OGD-treated neurons. Moreover, FTO mRNA expression was decreased in ferroptosis inducer, especially FAC. However, overexpression of FTO inhibited the ferroptosis of neurons. Moreover, FTO-mediated m6A modification of FTH1 suppressed its mRNA expression and stability, inhibiting its protein expression. However, overexpression of FTH1 abrogated the effects of FTO and promoted the ferroptosis of neurons. In summary, FTO functions as a protective role in neonatal HIE via inhibiting FTH1 signaling. Thence, targeting may be a promising strategy for FTO neonatal HIE.","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":null,"pages":null},"PeriodicalIF":1.5000,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Critical Reviews in Eukaryotic Gene Expression","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1615/critreveukaryotgeneexpr.2024054011","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
FTO is aberrantly expressed in brain disorders. However, the roles of FTO in neonatal hypoxic-ischemic brain injury (HIE) are still unclear. This study aims to investigate the potential of FTO in neonatal HIE. Oxygen-glucose deprivation (OGD) was used to establish HIE in vitro. mRNA levels were detected by RT-qPCR. Protein expression was detected by western blot. The levels of MDA, SOD, Fe2+ and GSH was detected by specific kit. m6A sites were analyzed using SRAMP and further verify by MeRIP assay. Cell proliferation was determined by CCK-8. Cell death was determined by PI staining. FTO was downregulated in patients with neonatal HIE and OGD-treated neurons. Moreover, FTO mRNA expression was decreased in ferroptosis inducer, especially FAC. However, overexpression of FTO inhibited the ferroptosis of neurons. Moreover, FTO-mediated m6A modification of FTH1 suppressed its mRNA expression and stability, inhibiting its protein expression. However, overexpression of FTH1 abrogated the effects of FTO and promoted the ferroptosis of neurons. In summary, FTO functions as a protective role in neonatal HIE via inhibiting FTH1 signaling. Thence, targeting may be a promising strategy for FTO neonatal HIE.
期刊介绍:
Critical ReviewsTM in Eukaryotic Gene Expression presents timely concepts and experimental approaches that are contributing to rapid advances in our mechanistic understanding of gene regulation, organization, and structure within the contexts of biological control and the diagnosis/treatment of disease. The journal provides in-depth critical reviews, on well-defined topics of immediate interest, written by recognized specialists in the field. Extensive literature citations provide a comprehensive information resource.
Reviews are developed from an historical perspective and suggest directions that can be anticipated. Strengths as well as limitations of methodologies and experimental strategies are considered.