{"title":"青蒿琥酯通过下调赖氨酸特异性去甲基酶5A抑制心肌缺血再灌注损伤","authors":"Yuanyuan Liu, Pengtao Zou, Yanmei Chen, Juanying Li, Qiang Liu, Qing Shangguan","doi":"10.1111/cbdd.70106","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>Myocardial ischemia–reperfusion (MI/R) injury can lead to heart disease. Meanwhile, Artesunate (ART) inhibits the severity of I/R-induced myocardial injury. Nevertheless, the underlying mechanism of ART in MI/R remains unclear. In vivo and in vitro experiments were performed to investigate the function of ART in MI/R. TTC, H&E, and TUNEL assays were applied for assessing myocardial injury and apoptosis. CCK-8, flow cytometry, and ELISA were applied for testing cell viability, apoptosis, and the levels of MDA, ROS, CK, and LDH, respectively. ChIP, dual luciferase assay, and RNA pull-down were performed to explore the relation among KDM5A, miR-495-3p, and FOXO1. ART dramatically attenuated I/R-induced myocardial injury in mice, and it inhibited the I/R-caused increase of ROS, MDA, CK, and LDH in mice. Additionally, ART notably alleviated hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury through inhibition of histone demethylase KDM5A, and KDM5A promoted H/R-induced injury in cardiomyocytes via downregulating miR-495-3p. Meanwhile, FOXO1 was identified as the downstream mRNA of miR-495-3p, and miR-495-3p reversed H/R-induced cardiomyocyte injury through downregulating FOXO1. Silencing of KDM5A attenuated I/R-induced myocardial injury by directly upregulating miR-495-3p in mice. ART alleviates MI/R injury via modulating KDM5A/miR-495-3p/FOXO1. Thus, this study might provide a new strategy against MI/R.</p>\n </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 6","pages":""},"PeriodicalIF":3.2000,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Artesunate Inhibits Myocardial Ischemia Reperfusion Injury via Downregulation of Lysine Specific Demethylase 5A\",\"authors\":\"Yuanyuan Liu, Pengtao Zou, Yanmei Chen, Juanying Li, Qiang Liu, Qing Shangguan\",\"doi\":\"10.1111/cbdd.70106\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <p>Myocardial ischemia–reperfusion (MI/R) injury can lead to heart disease. Meanwhile, Artesunate (ART) inhibits the severity of I/R-induced myocardial injury. Nevertheless, the underlying mechanism of ART in MI/R remains unclear. In vivo and in vitro experiments were performed to investigate the function of ART in MI/R. TTC, H&E, and TUNEL assays were applied for assessing myocardial injury and apoptosis. CCK-8, flow cytometry, and ELISA were applied for testing cell viability, apoptosis, and the levels of MDA, ROS, CK, and LDH, respectively. ChIP, dual luciferase assay, and RNA pull-down were performed to explore the relation among KDM5A, miR-495-3p, and FOXO1. ART dramatically attenuated I/R-induced myocardial injury in mice, and it inhibited the I/R-caused increase of ROS, MDA, CK, and LDH in mice. Additionally, ART notably alleviated hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury through inhibition of histone demethylase KDM5A, and KDM5A promoted H/R-induced injury in cardiomyocytes via downregulating miR-495-3p. Meanwhile, FOXO1 was identified as the downstream mRNA of miR-495-3p, and miR-495-3p reversed H/R-induced cardiomyocyte injury through downregulating FOXO1. Silencing of KDM5A attenuated I/R-induced myocardial injury by directly upregulating miR-495-3p in mice. ART alleviates MI/R injury via modulating KDM5A/miR-495-3p/FOXO1. Thus, this study might provide a new strategy against MI/R.</p>\\n </div>\",\"PeriodicalId\":143,\"journal\":{\"name\":\"Chemical Biology & Drug Design\",\"volume\":\"105 6\",\"pages\":\"\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2025-06-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Chemical Biology & Drug Design\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/cbdd.70106\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chemical Biology & Drug Design","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/cbdd.70106","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Artesunate Inhibits Myocardial Ischemia Reperfusion Injury via Downregulation of Lysine Specific Demethylase 5A
Myocardial ischemia–reperfusion (MI/R) injury can lead to heart disease. Meanwhile, Artesunate (ART) inhibits the severity of I/R-induced myocardial injury. Nevertheless, the underlying mechanism of ART in MI/R remains unclear. In vivo and in vitro experiments were performed to investigate the function of ART in MI/R. TTC, H&E, and TUNEL assays were applied for assessing myocardial injury and apoptosis. CCK-8, flow cytometry, and ELISA were applied for testing cell viability, apoptosis, and the levels of MDA, ROS, CK, and LDH, respectively. ChIP, dual luciferase assay, and RNA pull-down were performed to explore the relation among KDM5A, miR-495-3p, and FOXO1. ART dramatically attenuated I/R-induced myocardial injury in mice, and it inhibited the I/R-caused increase of ROS, MDA, CK, and LDH in mice. Additionally, ART notably alleviated hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury through inhibition of histone demethylase KDM5A, and KDM5A promoted H/R-induced injury in cardiomyocytes via downregulating miR-495-3p. Meanwhile, FOXO1 was identified as the downstream mRNA of miR-495-3p, and miR-495-3p reversed H/R-induced cardiomyocyte injury through downregulating FOXO1. Silencing of KDM5A attenuated I/R-induced myocardial injury by directly upregulating miR-495-3p in mice. ART alleviates MI/R injury via modulating KDM5A/miR-495-3p/FOXO1. Thus, this study might provide a new strategy against MI/R.
期刊介绍:
Chemical Biology & Drug Design is a peer-reviewed scientific journal that is dedicated to the advancement of innovative science, technology and medicine with a focus on the multidisciplinary fields of chemical biology and drug design. It is the aim of Chemical Biology & Drug Design to capture significant research and drug discovery that highlights new concepts, insight and new findings within the scope of chemical biology and drug design.