Iron promotes both ferroptosis and necroptosis in the early stage of reperfusion in ischemic stroke

作     者：Bin Du Zijie Deng Kang Chen Zhangzhong Yang Junfen Wei Liuyao Zhou Jie Meng Ying Cheng Xin Tian Qing-Zhang Tuo Peng Lei 

作者机构：Department of Neurology and State Key Laboratory of BiotherapyNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengduSichuan 610041China Department of NeurologyFirst Affiliated Hospital of Chongqing Medical UniversityChongqing Key Laboratory of NeurologyChongqing 400016China 

出 版 物：《Genes & Diseases》 (基因与疾病（英文）)

年 卷 期：2024年第11卷第6期

页      面：495-509页

核心收录：

学科分类：1002[医学-临床医学] 100204[医学-神经病学] 10[医学] 

基　　金：upported by the National Key Research and Development Program of China (No.2021YFC2500100) 1.3.5 Project for Disciplines of Excellence of West China Hospital of Sichuan University (No.ZYYC23016) the Key Research Projects of Sichuan Province,China (No.24SYSX0093) Major Science&Technology Program of Sichuan Province,China (No.2022ZDZX0021) the National Clinical Research Center for Geriatrics,West China Hospital,Sichuan University (China) (No.Z2023LC005) the Natural Science Foundation of Sichuan Province,China (No.2022NSFSC1509) the Fundamental Research Funds for the Central Universities (China) (No.2023SCU12074) 

主　　题：Deferoxamine Ferroptosis Iron Ischemic stroke Necroptosis 

摘      要：Programmed cell death contributes to neurological damage in ischemic stroke,especially during the reperfusion *** cell death pathways have been tested preclinically and clinically,including ferroptosis,necroptosis,and ***,the sequence and complex interplay between cell death pathways during ischemia/reperfusion remains under ***,we unbiasedly investigated cell death pathways during ischemia/reperfusion by utilizing RNA sequencing analysis and immunoblot assays and revealed that ferroptosis and necroptosis occurred early post-reperfusion,followed by *** inhibitor Liproxstatin-1 effectively inhibited necroptosis during reperfusion,while the necroptosis inhibitor Necrostatin-1 suppressed protein expression consistent with ferroptosis ***–protein interaction analysis and iron chelation therapy by deferoxamine mesylate indicate that iron is capable of promoting both ferroptosis and necroptosis in middle cerebral artery occlusion/repression modeled *** of cells with iron led to a disruption in redox balance with activated necroptosis and increased susceptibility to ***,these data uncovered a complex interplay between ferroptosis and necroptosis during ischemic stroke and indicated that multiple programmed cell death pathways may be targeted co-currently.