Inhibition of DNMT-1 alleviates ferroptosis through NCOA4 mediated ferritinophagy during diabetes myocardial ischemia/reperfusion injury

被引：119

作者：

Li, Wenyuan ^{[1
]}

Li, Wei ^{[1
]}

Wang, Yao ^{[2
]}

Leng, Yan ^{[1
]}

Xia, Zhongyuan ^{[1
]}

机构：

[1] Wuhan Univ, Renmin Hosp, Dept Anesthesiol, Wuhan, Peoples R China

[2] Wuhan Univ, Renmin Hosp, Dept Infect Dis, Wuhan, Peoples R China

来源：

CELL DEATH DISCOVERY | 2021年 / 7卷 / 01期

基金：

中国国家自然科学基金;

关键词：

CELL-DEATH; DNA METHYLATION; IRON; PEROXIDATION;

D O I：

10.1038/s41420-021-00656-0

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The purpose of this study was to investigate whether inhibition of DNA (cytosine-5)-methyltransferase 1 (DNMT-1) alleviated ferroptosis through nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy during diabetes myocardial (DM) ischemia/reperfusion (I/R) injury (IRI). Rat DM + sham (DS), I/R, and DM + I/R (DIR), H9c2 cell high glucose (HG), hypoxia reoxygenation (H/R), and high-glucose hypoxia reoxygenation (HH/R) models were established. DNMT-1 inhibitor 5-Aza-2'-deoxycytidine (5-aza-CdR) was administered to rat and cell models. The protein level of DNMT-1, NCOA4, FTH, GPX4, Beclin-1, and P62 was detected by western blotting. Compared with normal sham (NS) group, myocardial tissue was injured in DS and I/R models. The level of DNMT-1, NCOA4, and ferroptosis was increased. Moreover, the cell injury was more serious in rat DIR or HH/R model. 5-Aza-CdR could reduce NCOA4-mediated ferritinophagy and myocardial injury in DIR and HH/R models. Moreover, the siRNA for NCOA4 could also reduce the level of ferritinophagy and cell injury in HH/R model. 5-Aza-CdR enhanced the protective effect for NCOA4-siRNA in the process of cell injury. Inhibition of DNMT-1 could reduce ferroptosis during DIR, which the NCOA4-mediated ferritinophagy might be regulated.

引用

页数：14

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