title: Heat shock protein 70 inhibits cardiomyocyte necroptosis through repressing autophagy in myocardial ischemia/reperfusion injury.
abstract: Irreversible damage of cardiac function arisen from myocardial ischemia/reperfusion injury (MIRI) leads to an emerging challenge in the treatments of cardiac ischemic diseases. Molecular chaperone heat shock protein 70 (HSP70) attenuates heat-stimulated cell autophagy, apoptosis, and damage in the heart. Under specific conditions, autophagy may, directly or indirectly, induce cell death including necroptosis. Whether HSP70 inhibits cardiomyocyte necroptosis via suppressing autophagy during MIRI is unknown. In our study, HSP70 expression was opposite to necroptosis marker RIP1 and autophagy marker LC3A/B expression after myocardial ischemia/reperfusion (MIR) in vivo. Furthermore, in vitro primary rat cardiomyocytes mimicked MIRI by hypoxia/reoxygenation (H/R) treatment. Knockdown of HSP70 expression promoted cardiomyocyte autophagy and necroptosis following H/R treatment, while the increase tendency was downregulated by autophagy inhibitor 3-MA, showing that autophagy-induced necroptosis could be suppressed by HSP70. In summary, HSP70 downregulates cardiomyocyte necroptosis through suppressing autophagy during myocardial IR, revealing the novel protective mechanism of HSP70 and supplying a novel molecular target for the treatment of heart ischemic diseases.
authors.affiliation: Department of Pathogen Biology, Medical College, Nantong University, Nantong, Jiangsu, 226001, People's Republic of China.|Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, Jiangsu, 226001, People's Republic of China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, Jiangsu, 226001, People's Republic of China.|Department of Cardiology, Affiliated Hospital of Nantong University, Nantong, 226001, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, Jiangsu, 226001, People's Republic of China.|Department of Cardiology, Affiliated Hospital of Nantong University, Nantong, 226001, People's Republic of China.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, Jiangsu, 226001, People's Republic of China.|Department of Cardiology, Affiliated Hospital of Nantong University, Nantong, 226001, People's Republic of China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Li
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, Jiangsu, 226001, People's Republic of China.|Department of Cardiology, Affiliated Hospital of Nantong University, Nantong, 226001, People's Republic of China.
authors.forename: Wanwan
authors.initials: W
authors.lastname: Guo
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, Jiangsu, 226001, People's Republic of China.|Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226001, People's Republic of China.
authors.forename: Daliang
authors.initials: D
authors.lastname: Yan
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, Jiangsu, 226001, People's Republic of China.|Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226001, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Yang
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, Jiangsu, 226001, People's Republic of China.|Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226001, People's Republic of China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Pathogen Biology, Medical College, Nantong University, Nantong, Jiangsu, 226001, People's Republic of China.
authors.forename: Tian
authors.initials: T
authors.lastname: Xia
authors.affiliation: Department of Pathogen Biology, Medical College, Nantong University, Nantong, Jiangsu, 226001, People's Republic of China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathogen Biology, Medical College, Nantong University, Nantong, Jiangsu, 226001, People's Republic of China.
authors.forename: Rong
authors.initials: R
authors.lastname: Xu
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, Jiangsu, 226001, People's Republic of China. ntwx0513@163.com.|Department of Cardiology, Affiliated Hospital of Nantong University, Nantong, 226001, People's Republic of China. ntwx0513@163.com.
authors.forename: Xiang
authors.initials: X
authors.lastname: Wu
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, Jiangsu, 226001, People's Republic of China. ntsjh0513@163.com.|Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226001, People's Republic of China. ntsjh0513@163.com.
authors.forename: Jiahai
authors.initials: J
authors.lastname: Shi
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology; D015687:Cell Hypoxia; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D018840:HSP70 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D007150:Immunohistochemistry; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology*; D009336:Necrosis / Q000503:physiopathology; D017346:Protein Serine-Threonine Kinases; D051381:Rats; D017207:Rats, Sprague-Dawley; D053422:Receptor-Interacting Protein Serine-Threonine Kinases
chemical_list: D018840:HSP70 Heat-Shock Proteins; D008869:Microtubule-Associated Proteins; D017346:Protein Serine-Threonine Kinases; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C526109:Anxa3 protein, rat; C586536:RIPK1 protein, rat
keywords: Autophagy; HSP70; Myocardial ischemia/reperfusion injury; Necroptosis