Yihua Wang, Qiang Yue, Xiurong Song, Wei Du, Rui Liu
{"title":"缺氧/再氧诱导糖酵解通过促进GPX4的乳酸化介导心肌缺血再灌注损伤。","authors":"Yihua Wang, Qiang Yue, Xiurong Song, Wei Du, Rui Liu","doi":"10.1007/s12265-025-10628-9","DOIUrl":null,"url":null,"abstract":"<p><p>Myocardial ischemia-reperfusion injury (MIRI) is an injury mechanism of myocardial infarction, related to ferroptosis and glycolysis. Lactate produced by glycolysis promotes protein lactylation. This study aimed to investigate the correlation between glycolysis, ferroptosis, and GPX4 lactylation in MIRI. Hypoxia/reoxygenation (H/R) increased glucose uptake, lactate production, ECAR, OCR, LDH release, lipid ROS, Fe<sup>2+</sup>, GSH, MDA contents, and cell apoptosis, and decreased GSH level in the H9C2 cells, suggesting H/R promoted glycolysis and ferroptosis. 2-DG treatment relieved the H/R-induced injury, while lactate treatment aggravated it. Besides, 2-DG suppressed lactylation of GPX4 at K218 and K228 sites and increased its protein stability. GPX4 overexpression relieved the injury caused by H/R, and alleviated cardiac injury, decreased cardiomyocyte ferroptosis in heart tissues of MIRI rats. In conclusion, GPX4 lactylation facilitated H/R-induced cardiomyocyte injury and aggravated MIRI in rats. Our findings provided new insight into targeting glycolysis and GPX4 lactylation as therapeutic strategies of MIRI.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":""},"PeriodicalIF":2.4000,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Hypoxia/reoxygenation-induced Glycolysis Mediates Myocardial Ischemia-reperfusion Injury Through Promoting the Lactylation of GPX4.\",\"authors\":\"Yihua Wang, Qiang Yue, Xiurong Song, Wei Du, Rui Liu\",\"doi\":\"10.1007/s12265-025-10628-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Myocardial ischemia-reperfusion injury (MIRI) is an injury mechanism of myocardial infarction, related to ferroptosis and glycolysis. Lactate produced by glycolysis promotes protein lactylation. This study aimed to investigate the correlation between glycolysis, ferroptosis, and GPX4 lactylation in MIRI. Hypoxia/reoxygenation (H/R) increased glucose uptake, lactate production, ECAR, OCR, LDH release, lipid ROS, Fe<sup>2+</sup>, GSH, MDA contents, and cell apoptosis, and decreased GSH level in the H9C2 cells, suggesting H/R promoted glycolysis and ferroptosis. 2-DG treatment relieved the H/R-induced injury, while lactate treatment aggravated it. Besides, 2-DG suppressed lactylation of GPX4 at K218 and K228 sites and increased its protein stability. GPX4 overexpression relieved the injury caused by H/R, and alleviated cardiac injury, decreased cardiomyocyte ferroptosis in heart tissues of MIRI rats. In conclusion, GPX4 lactylation facilitated H/R-induced cardiomyocyte injury and aggravated MIRI in rats. Our findings provided new insight into targeting glycolysis and GPX4 lactylation as therapeutic strategies of MIRI.</p>\",\"PeriodicalId\":15224,\"journal\":{\"name\":\"Journal of Cardiovascular Translational Research\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2025-06-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Cardiovascular Translational Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s12265-025-10628-9\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Cardiovascular Translational Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12265-025-10628-9","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
Hypoxia/reoxygenation-induced Glycolysis Mediates Myocardial Ischemia-reperfusion Injury Through Promoting the Lactylation of GPX4.
Myocardial ischemia-reperfusion injury (MIRI) is an injury mechanism of myocardial infarction, related to ferroptosis and glycolysis. Lactate produced by glycolysis promotes protein lactylation. This study aimed to investigate the correlation between glycolysis, ferroptosis, and GPX4 lactylation in MIRI. Hypoxia/reoxygenation (H/R) increased glucose uptake, lactate production, ECAR, OCR, LDH release, lipid ROS, Fe2+, GSH, MDA contents, and cell apoptosis, and decreased GSH level in the H9C2 cells, suggesting H/R promoted glycolysis and ferroptosis. 2-DG treatment relieved the H/R-induced injury, while lactate treatment aggravated it. Besides, 2-DG suppressed lactylation of GPX4 at K218 and K228 sites and increased its protein stability. GPX4 overexpression relieved the injury caused by H/R, and alleviated cardiac injury, decreased cardiomyocyte ferroptosis in heart tissues of MIRI rats. In conclusion, GPX4 lactylation facilitated H/R-induced cardiomyocyte injury and aggravated MIRI in rats. Our findings provided new insight into targeting glycolysis and GPX4 lactylation as therapeutic strategies of MIRI.
期刊介绍：
Journal of Cardiovascular Translational Research (JCTR) is a premier journal in cardiovascular translational research.
JCTR is the journal of choice for authors seeking the broadest audience for emerging technologies, therapies and diagnostics, pre-clinical research, and first-in-man clinical trials.
JCTR''s intent is to provide a forum for critical evaluation of the novel cardiovascular science, to showcase important and clinically relevant aspects of the new research, as well as to discuss the impediments that may need to be overcome during the translation to patient care.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
