Inhibition of DNMT-1 alleviates ferroptosis through NCOA4 mediated ferritinophagy during diabetes myocardial ischemia/reperfusion injury.
Inhibition of DNMT-1 alleviates ferroptosis through NCOA4 mediated ferritinophagy during diabetes myocardial ischemia/reperfusion injury.
复制标题
糖尿病心肌缺血/再灌注损伤期间，抑制 DNMT-1 通过 NCOA4 介导的铁蛋白自噬减轻铁死亡
DOI：
10.1038/s41420-021-00656-0
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发表时间：
2021-09-29
影响因子：
7
通讯作者：
Xia Z
中科院分区：
文献类型：
--
作者：
Li W;Li W;Wang Y;Leng Y;Xia Z
本研究旨在探讨DNA（胞嘧啶-5）-甲基转移酶1 （DNMT-1）的抑制是否通过核受体共激活因子4 （NCOA4）介导的铁蛋白吞噬在糖尿病心肌（DM）缺血/再灌注（I/R）损伤（IRI）中减轻铁凋亡。建立大鼠DM + sham （DS）、I/R、DM + I/R （DIR）、H9c2细胞高糖（HG）、缺氧再氧（H/R）、高糖缺氧再氧（HH/R）模型。DNMT-1抑制剂5-Aza-2 ' -脱氧胞苷（5-aza-CdR）给予大鼠和细胞模型。western blotting检测DNMT-1、NCOA4、FTH、GPX4、Beclin-1、P62蛋白水平。与正常假手术（NS）组比较，DS和I/R模型心肌组织均受损。DNMT-1、NCOA4、铁下垂水平升高。而且，大鼠DIR和HH/R模型的细胞损伤更为严重。5-Aza-CdR可减轻ncoa4介导的铁蛋白吞噬和心肌损伤。此外，NCOA4的siRNA也可以降低HH/R模型中铁蛋白自噬水平和细胞损伤。5-Aza-CdR在细胞损伤过程中增强了对NCOA4-siRNA的保护作用。抑制DNMT-1可减少DIR期间铁下垂，ncoa4介导的铁蛋白自噬可能受到调控。
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.
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影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
3.7
作者：
Nguyen A;Mamarbachi M;Turcot V;Lessard S;Yu C;Luo X;Lalongé J;Hayami D;Gayda M;Juneau M;Thorin-Trescases N;Lettre G;Nigam A;Thorin E
通讯作者：
Thorin E
影响因子：
64.8
作者：
Mancias, Joseph D.;Wang, Xiaoxu;Gygi, Steven P.;Harper, J. Wade;Kimmelman, Alec C.
通讯作者：
Kimmelman, Alec C.
DOI：
10.1152/ajplung.00161.2016
发表时间：
2016-11-01
影响因子：
4.9
作者：
Li, Yunxiao;Yu, Ganggang;Wang, Haoyan
通讯作者：
Wang, Haoyan
影响因子：
21.3
作者：
Friedmann Angeli JP;Schneider M;Proneth B;Tyurina YY;Tyurin VA;Hammond VJ;Herbach N;Aichler M;Walch A;Eggenhofer E;Basavarajappa D;Rådmark O;Kobayashi S;Seibt T;Beck H;Neff F;Esposito I;Wanke R;Förster H;Yefremova O;Heinrichmeyer M;Bornkamm GW;Geissler EK;Thomas SB;Stockwell BR;O'Donnell VB;Kagan VE;Schick JA;Conrad M
通讯作者：
Conrad M