ALOX15-launched PUFA-phospholipids peroxidation increases the susceptibility of ferroptosis in ischemia-induced myocardial damage
作者机构：Guangdong Engineering Research Center of Chinese Medicine&Disease SusceptibiltyJinan UniversityGuangzhou 510632China Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs ResearchCollege of PharmacyJinan UniversityGuangzhou 510632China international Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education(MOE)Jinan UniversityGuangzhou 510632China institute of Traditional Chinese MedicineXinjiang Medical UniversityUrumqi 830054China Sinnovation Center of Nursing ResearchNursing Key Laboratory of Sichuan ProvinceState Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityChengdu 610041China College of PharmacyGuangzhou University of Chinese Medicine Guangzhou 510405China Key Laboratory of Chinese Internal Medicine of Ministry of EducationDongzhimen HospitalBeijing University of Chinese Medicine100700 BeijingChina
出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)
年 卷 期：2022年第7卷第9期
页 面：3523-3535页
核心收录：
学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
基 金：This work was supported,in part,by National Key Research and Development Program of China(2017YFC1700400,2017YFC1700404,2022YFC0867400) Natural Science Foundation of China(82125038,81904068,81873209,U1801284,81903821,82174054) the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(2017BT01 Y036) GDUPS(2019),Natural Science Foundation of Guangdong(2019A1515010909,2021A1515011297) Science and Technology Program of Guangzhou(201903010062,907158833068) the Innovation Team Project of Guangdong Provincial Department of Education(2020KCXTD003)
主 题：peroxidation ischemia damage
摘 要：Myocardial ischemia/reperfusion(/R)injury is a classic type of cardiovascular disease characterized by injury to cardiomyocytes leading to various forms of cell *** is believed that irreversible myocardial damage resulted from I/R occurs due to oxidative stress evoked during the reperfusion *** we demonstrate that ischemia triggers a specific redox reaction of polyunsaturated fatty acids(PUFA)-phospholipids in myocardial cells,which acts as a priming signaling that initiates the outbreak of robust oxidative damage in the reperfusion *** animal and in vitro models,the crucial lipid species in I/R injury were identifed to be oxidized PUFAs enriched *** multi-omics,arachidonic acid 15-lipoxygenase-1(ALOx15)was identified as the primary mediator of ischemia-provoked phospholipid peroxidation,which was further confirmed using chemogenetic ***,our results reveal that ALOx15 induction in the ischemia phase acts as aburning pointto ignite phospholipid oxidization into ferroptotic *** finding characterizes a novel molecular mechanism for myocardial ischemia injury and offers a potential therapeutic target for early intervention of V/R injury.
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