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
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页数:12
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