中国病理生理杂志2025，Vol.41Issue(4)：653-660,8.DOI:10.3969/j.issn.1000-4718.2025.04.004
MG53蛋白乳酸化修饰通过介导心肌细胞铁死亡加重小鼠心肌缺血再灌注损伤
Lactylation of MG53 protein enhances mouse myocardial ischemia/reper-fusion injury by mediating cardiomyocyte ferroptosis
摘要
Abstract
AIM:This study aims to investigate the changes in the lactylation levels of mitsugumin 53(MG53)protein during myocardial ischemia/reperfusion(I/R)and to further explore the potential molecular mechanisms by which MG53 lactylation impacts myocardial cell injury resulting from I/R.METHODS:A myocardial I/R model was established in mice through ligation of the left anterior descending coronary artery followed by reperfusion.Simultaneous-ly,a hypoxia/reoxygenation(H/R)model of rat myocardial H9C2 cells was created in vitro.In the mouse model,TTC and HE staining were employed to assess myocardial ischemia and injury.The levels of creatine kinase and cardiac troponin I were quantified using ELISA,while MG53 expression was evaluated through immunofluorescence.In the in vitro cell model,CCK-8 assay and flow cytometry were utilized to measure cell viability and apoptosis level,respectively.The levels of MG53 protein,its lactylation,and ferroptosis-related proteins in both mouse myocardial tissue and in vitro rat cardiomyo-cytes were analyzed using immunoprecipitation and Western blot.Additionally,the levels of reactive oxygen species,fer-rous ion,lactate dehydrogenase and malondialdehyde in tissues and cells were measured using appropriate assay kits.RE-SULTS:In the I/R group,mouse myocardial tissue exhibited significant injury following cardiac I/R.The expression of MG53 protein was reduced,while the lactylation level of MG53 protein and the ferroptosis of myocardial cells were in-creased.In the in vitro cardiomyocyte experiments,H/R exposure resulted in decreased cell viability,increased apoptosis and ferroptosis levels,reduced MG53 protein expression,and increased MG53 lactylation level.Treatment with 2-deoxy-D-glucose(2-DG)improved cardiomyocyte viability,decreased apoptosis and ferroptosis levels,increased MG53 expres-sion,and lowered MG53 lactylation level.Furthermore,the addition of exogenous lactate significantly countered the ef-fects of 2-DG on cell viability and MG53 expression,and increased the cell apoptosis,ferroptosis and MG53 lactylation levels.CONCLUSION:During myocardial I/R,there is a down-regulation of MG53 protein expression accompanied by an increase in the lactylation level of MG53 protein.The elevation of MG53 lactylation may exacerbate myocardial I/R inju-ry by facilitating the ferroptosis of cardiomyocytes.关键词
心肌缺血/再灌注损伤/铁死亡/MG53蛋白/非组蛋白乳酸化Key words
myocardial ischemia/reperfusion injury/ferroptosis/MG53 protein/non-histone lactylation分类
临床医学引用本文复制引用
李小旺,方飞,陆建忠,强鑫华,卢凯,廖俊..MG53蛋白乳酸化修饰通过介导心肌细胞铁死亡加重小鼠心肌缺血再灌注损伤[J].中国病理生理杂志,2025,41(4):653-660,8.基金项目
湖州市科技计划公益性应用研究项目(No.2023GY23) （No.2023GY23）
