title: WDR26 promotes mitophagy of cardiomyocytes induced by hypoxia through Parkin translocation.
abstract: Myocardial ischemia is a heart condition caused by reduction of blood flow to the heart, preventing heart from receiving enough oxygen. Myocardial ischemia is the most common cause of death globally. Heart ischemic preconditioning (IPC) has a protective effect against myocardial cell death induced by ischemia and ischemia-reperfusion injury. WDR26 has recently been identified as a protein that is increased following rat cardiac IPC. WDR26 can promote the proliferation of H9c2 cells and protect cardiomyocytes against oxidative stress through inhibiting apoptosis. However, its role in myocardial ischemia is unclear. The aim of this study was to explore the role of WDR26 in myocardial ischemia and H9c2 cell hypoxia. Our results showed that WDR26 is induced by myocardial ischemia and H9c2 cell hypoxia. WDR26 protects H9c2 cells against hypoxia injury through inhibiting LDH release and increasing cell viability. WDR26 promotes hypoxia-induced autophagy in hypoxia of H9c2 cells. We further demonstrated that in H9c2 cell hypoxia, WDR26 increases mitochondrial membrane potential, thereby increases Parkin translocation of mitochondria. After Parkin is translocated at mitochondria, WDR26 can increase mitochondrial protein ubiquitination in hypoxia of H9c2 cells. WDR26 is a mediator of response to hypoxia, and WDR26 plays an important role in hypoxia-mediated autophagy and mitophagy. This study provides novel insights into the protective role of WDR26 in cardiomyocyte injury during hypoxia. WDR26 may serve as a potential target for the treatment of myocardial ischemia.
authors: Department of Pathophysiology, Xinxiang Medical University, Xinxiang 453003, China.
authors: Yansheng
authors: Y
authors: Feng
authors: Department of Pathophysiology, Xinxiang Medical University, Xinxiang 453003, China.
authors: Jia
authors: J
authors: Zhao
authors: Department of Pathophysiology, Xinxiang Medical University, Xinxiang 453003, China.|Department of Pathophysiology, West China School of Preclinical Sciences and Forensic Medicine, Sichuan University, Chengdu 610041, China.
authors: Huifang
authors: H
authors: Hou
authors: School of Nursing, Xinxiang Medical University, Xinxiang 453003, China.
authors: Hui
authors: H
authors: Zhang
authors: Department of Pathology, Xinxiang Medical University, Xinxiang 453003, China.|Department of Histology and Embryology, School of Basic Medical Sciences, Central South University, Changsha 410008, China.
authors: Yunjuan
authors: Y
authors: Jiao
authors: Department of Pathophysiology, Xinxiang Medical University, Xinxiang 453003, China.
authors: Jiangang
authors: J
authors: Wang
authors: Department of Pathophysiology, Xinxiang Medical University, Xinxiang 453003, China 011025@xxmu.edu.cn sypxxmu@sina.com.
authors: Yongling
authors: Y
authors: Wang
authors: Department of Pathophysiology, Xinxiang Medical University, Xinxiang 453003, China 011025@xxmu.edu.cn sypxxmu@sina.com.
authors: Yinping
authors: Y
authors: Sun
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D002460:Cell Line; D053078:Membrane Potential, Mitochondrial; D063306:Mitophagy / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D021381:Protein Transport; D011506:Proteins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D011506:Proteins; C000613819:WDR26 protein, rat; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein
keywords: WDR26; autophagy; hypoxia; mitophagy; myocardial ischemia