ALOX15-launched PUFA-phospholipids peroxidation increases the susceptibility of ferroptosis in ischemia-induced myocardial damage  

作　　者：Xiao-Hui Ma Jiang-Han-Zi Liu Chun-Yu Liu Wan-Yang Sun Wen-Jun Duan Guan Wang Hiroshi Kuriara Rong-Rong He Yi-Fang Li Yang Chen Hongcai Shang 

机构地区：[1]Guangdong Engineering Research Center of Chinese Medicine&Disease Susceptibilty,Jinan University,Guangzhou 510632,China [2]Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research,College of Pharmacy,Jinan University,Guangzhou 510632,China [3]international Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education(MOE),Jinan University,Guangzhou 510632,China [4]institute of Traditional Chinese Medicine,Xinjiang Medical University,Urumqi 830054,China [5]Sinnovation Center of Nursing Research,Nursing Key Laboratory of Sichuan Province,State Key Laboratory of Biotherapy and Cancer Center,West China Hospital,Sichuan University,Chengdu 610041,China [6]College of Pharmacy,Guangzhou University of Chinese Medicine Guangzhou 510405,China [7]Key Laboratory of Chinese Internal Medicine of Ministry of Education,Dongzhimen Hospital,Beijing University of Chinese Medicine,100700 Beijing,China

出　　处：《Signal Transduction and Targeted Therapy》2022年第9期3523-3535,共13页信号转导与靶向治疗（英文）

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).

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 death.It is believed that irreversible myocardial damage resulted from I/R occurs due to oxidative stress evoked during the reperfusion phase.Here 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 phase.Using animal and in vitro models,the crucial lipid species in I/R injury were identifed to be oxidized PUFAs enriched phosphatidylethanolamines.Using 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 approaches.Collectively,our results reveal that ALOx15 induction in the ischemia phase acts as a"burning point"to ignite phospholipid oxidization into ferroptotic signals.This finding characterizes a novel molecular mechanism for myocardial ischemia injury and offers a potential therapeutic target for early intervention of V/R injury.

关 键 词：PEROXIDATION ISCHEMIA damage 

分 类 号：R542.2[医药卫生—心血管疾病]