FTO-Mediated m6A Modification of FTH1 Inhibits Ferroptosis of Neurons in Neonatal Cerebral Hypoxic Ischemia

被引:0
|
作者
Chen, Yanhong [1 ]
Huang, Jia [2 ]
机构
[1] Nantong Univ, Affiliated Hosp 2, Pediat Dept, Nantong 226006, Jiangsu, Peoples R China
[2] Nantong Univ, Affiliated Matern & Child Hlth Care Hosp, Child Hlth Dept, 399 Century Ave, Nantong 226006, Jiangsu, Peoples R China
来源
CRITICAL REVIEWS IN EUKARYOTIC GENE EXPRESSION | 2024年 / 34卷 / 08期
关键词
neonatal hypoxic-ischemic brain injury; FTO alpha-ketoglutarate dependent dioxygenase; N6-methyladenosine; ferritin heavy chain 1; ferroptosis; INJURY;
D O I
暂无
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
FTO alpha-ketoglutarate dependent dioxygenase (FTO) is aberrantly expressed in brain disorders. How-ever, 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 real-time reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). Protein expression was detected by Western blot. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), ferrous iron (Fe2+) and glutathione (GSH) was detected by specific kit. m6A sites were analyzed using SRAMP and further verify by meth-ylated RNA immunoprecipitation (MeRIP) assay. Cell proliferation was determined by Cell Counting Kit-8 (CCK-8) assay. Cell death was determined by propidium iodide (PI) staining. FTO was downregulated in patients with neonatal HIE and OGD-treated neurons. Moreover, FTO mRNA expression was decreased in ferroptosis inducer, especially ferric ammonium citrate (FAC). However, overexpression of FTO inhibited the ferroptosis of neurons. Moreover, FTO-me-diated N6-methyladenosine (m6A) modification of ferritin heavy chain 1 (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
引用
收藏
页数:12
相关论文
共 50 条
  • [1] Bisphenol F induces spermatogenic cell ferroptosis via FTO-mediated m6A regulation of FTH1
    Zhou, Shi-meng
    Shi, Yu
    Li, Jiang-ying
    Wang, Na
    Zeng, Yong
    Chen, Hong-qiang
    Tan, Yu-pei
    Deng, Shuang-wu
    Liu, Qing-qing
    Huang, Xin-qiao
    Wang, Yi-qi
    Zhou, Zi-yuan
    Liu, Wen-bin
    FREE RADICAL BIOLOGY AND MEDICINE, 2025, 229 : 364 - 373
  • [2] The Interplay between FTO-Mediated m6A Demethylation and Ferroptosis in the Development of Diabetic Retinopathy
    Jiao, Wanzhen
    Liu, Weiwei
    Xu, Wenwen
    Meng, Xiaoqun
    Yu, Miao
    Ji, Jiafu
    JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS, 2024, 38 (02): : 1711 - 1722
  • [3] FTO-mediated m6A modification of SOCS1 mRNA promotes the progression of diabetic kidney disease
    Sun, Qiangr
    Geng, Houfa
    Zhao, Meng
    Li, Yang
    Chen, Xi
    Sha, Qian
    Lai, Peng
    Tang, Daoquan
    Yang, Dongzhi
    Liang, Jun
    Guo, Mengzhe
    CLINICAL AND TRANSLATIONAL MEDICINE, 2022, 12 (06):
  • [4] FTO-mediated SMAD2 m6A modification protects cartilage against Osteoarthritis
    Zhou, Hongyi
    Xie, Ziang
    Qian, Yu
    Ni, Weiyu
    Cui, Lei
    Fang, Xiangqian
    Wan, Shuanglin
    Zhao, Xiangde
    Qin, An
    Fan, Shunwu
    Wu, Yizheng
    EXPERIMENTAL AND MOLECULAR MEDICINE, 2024, 56 (10): : 2283 - 2295
  • [5] GIV/Girdin Modulation of Microglial Activation in Ischemic Stroke: Impact of FTO-Mediated m6A Modification
    Xie, Peng
    Xia, Mingyan
    Long, Tingting
    Guo, Dongfen
    Cao, Wenpeng
    Sun, Ping
    Yu, Wenfeng
    MOLECULAR NEUROBIOLOGY, 2024, : 5501 - 5517
  • [6] GnRH-driven FTO-mediated RNA m6A modification promotes gonadotropin synthesis and secretion
    Wang, Hao-Qi
    Ma, Yi-Ran
    Zhang, Yu-Xin
    Wei, Fan-Hao
    Zheng, Yi
    Ji, Zhong-Hao
    Guo, Hai-Xiang
    Wang, Tian
    Zhang, Jia-Bao
    Yuan, Bao
    BMC BIOLOGY, 2024, 22 (01)
  • [7] IDO1 inhibits ferroptosis by regulating FTO-mediated m6A methylation and SLC7A11 mRNA stability during glioblastoma progression
    Tian, Qianting
    Dan, Guixue
    Wang, Xuyan
    Zhu, Jiamei
    Chen, Chaochun
    Tang, Dekun
    Wang, Ziming
    Chen, Dan
    Lei, Shan
    Yang, Chao
    Wang, Houmei
    Guo, Bing
    Jin, Bangming
    Chen, Tengxiang
    Tang, Lei
    CELL DEATH DISCOVERY, 2025, 11 (01)
  • [8] Suppression of TLR4 prevents diabetic bone loss by regulating FTO-mediated m6A modification
    Shen, Ximei
    Lan, Chao
    Lin, Youfen
    Zhang, Fuyashi
    Zhang, Yongze
    Chen, Mingyun
    Yan, Sunjie
    INTERNATIONAL IMMUNOPHARMACOLOGY, 2023, 122
  • [9] Demethylase FTO-mediated m6A modification of SIK1 modulates placental cytotrophoblast syncytialization in type 2 diabetes mellitus
    Ning, Jie
    Yan, Jie
    Wang, Shuxian
    Cui, Zifeng
    Xue, Yiwei
    Juan, Juan
    Yang, Huixia
    ISCIENCE, 2024, 27 (06)
  • [10] FTO-mediated RNA m6A 6 A methylation regulates synovial aggression and inflammation in rheumatoid arthritis
    Li, Ruiru
    Kuang, Yu
    Niu, Yuanyuan
    Zhang, Shuoyang
    Chen, Simin
    Su, Fan
    Wang, Jingnan
    Lin, Shuibin
    Liu, Di
    Shen, Chuyu
    Liang, Liuqin
    Zheng, Song Guo
    Jie, Ligang
    Xiao, Youjun
    Xu, Hanshi
    BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2024, 1870 (07):