Involvement of phosphatase and tensin homolog-induced putative kinase 1–Parkin-mediated mitophagy in septic acute kidney injury

作     者：Xin-Gui Dai Wei Xu Tao Li Jia-Ying Lu Yang Yang Qiong Li Zhen-Hua Zeng Yu-Hang Ai Dai Xin-Gui;Xu Wei;Li Tao;Lu Jia-Ying;Yang Yang;Li Qiong;Zeng Zhen-Hua;Ai Yu-Hang

作者机构：Department of Intensive Care UnitXiangya HospitalCentral South UniversityChangshaHunan 410078China Department of Critical Care MedicineThe First People's Hospital of ChenzhouChenzhouHunan 423000China Department of Critical Care MedicineNanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China 

出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)

年 卷 期：2019年第132卷第19期

页      面：2340-2347页

核心收录：

学科分类：1002[医学-临床医学] 100210[医学-外科学(含：普外、骨外、泌尿外、胸心外、神外、整形、烧伤、野战外)] 10[医学] 

基　　金：This work was supported by grants from the National Natural Science Foundation of China(Nos.81601708,81671960) the Natural Science Foundation of Hunan Province,China(No.2018JJ2014) 

主　　题：Sepsis Acute kidney injury Autophagy Mitophagy Phosphatase and tensin homolog-induced putative kinase 1 E3 ubiquitin-protein ligase Parkin 

摘      要：Background:Studies have reported mitophagy activation in renal tubular epithelial cells(RTECs)in acute kidney injury(AKI).Phosphatase and tensin homolog-induced putative kinase 1(PINK1)and E3 ubiquitin-protein ligase Parkin are involved in mitophagy regulation;however,little is known about the role of PINK1-Parkin mitophagy in septic *** we investigated whether the PINK1-Parkin mitophagy pathway is involved in septic AKI and its effects on cell apoptosis in vitro and on renal functions in ***:Mitophagy-related gene expression was determined using Western blot assay in human RTEC cell line HK-2 stimulated with bacterial lipopolysaccharide(LPS)and in RTECs from septic AKI rats induced by cecal ligation and perforation(CLP).Autophagy-related ultrastructural features in rat RTECs were observed using electron ***-and loss-of-function approaches were performed to investigate the role of the PINK1-Parkin pathway in HK-2 cell *** activators and inhibitors were used to assess the effects of mitophagy modulation on cell apoptosis in vitro and on renal functions in ***:LPS stimulation could significantly induce LC3-II and BECN-1 protein expression(LC3-II:1.72±0.05 vs.1.00±0.05,P0.05;BECN-1:5.33±0.57 vs.1.00±0.14,P0.05)at 4 h in ***,LC3-II,and BECN-1 protein levels were significantly increased and peaked at 2 h after CLP(LC3-II:3.33±0.12 vs.1.03±0.15,P0.05;BECN-1:1.57±0.26 vs.1.02±0.11,P0.05)in vivo compared with those after sham *** deformation and mitolysosome-mediated mitochondria clearance were observed in RTECs from septic ***1 knockdown significantly attenuated LC3-II protein expression(1.35±0.21 vs.2.38±0.22,P0.05),whereas PINK1 overexpression markedly enhanced LC3-II protein expression(2.07±0.21 vs.1.29±0.19,P0.05)compared with LPS-stimulated HK-2 ***-induced proapoptotic protein expression remained unchanged in autophagy activator-treated HK-2 cells and was significantl