title: MG53 anchored by dysferlin to cell membrane reduces hepatocyte apoptosis which induced by ischaemia/reperfusion injury in vivo and in vitro.
abstract: Hepatic ischaemia/reperfusion (HIR) induces severe damage on hepatocyte cell membrane, which leads to hepatocyte death and the subsequent HIR injury. In this study, we investigated the role and the mechanism of mitsugumin-53 (MG53), a novel cell membrane repair protein, in protecting the liver against HIR injury. Rats were subjected to sham operation or 70% warm HIR with or without recombined MG53 (rhMG53), caudal vein-injected 2 hrs before inducing HIR. In vitro, cultured hepatocyte AML12 cells were subjected to hypoxia/reoxygenation (H/R) in the presence of rhMG53 and/or dysferlin gene shRNAs or adenovirus transfection. HIR resulted in severe liver injury manifested as severe liver histological changes and increased AST and ALT release. Post-ischaemic hepatic oxidative stress was significantly enhanced demonstrated by elevated dihydroethidium level, increased 4-hydroxynonenal, enhanced 15-F2t-isoprostane and decreased SOD activity. rhMG53 administration attenuated post-HIR liver injury, decreased liver oxidative stress and further enhanced dysferlin protein expression and its colocalization with MG53. Similarly, H/R induced AML12 cell injury and oxidative stress, which were abolished by either rhMG53 or dysferlin overexpression but were exacerbated by dysferlin gene knockdown. Dysferlin overexpression further increased H/R-induced increased colocalization of MG53 and dysferlin. In conclusion, MG53 was anchored by dysferlin to reduce oxidative stress and cell death and attenuate HIR injury.
authors.affiliation: Department of Anesthesiology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Yao
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China.|Department of Anaesthesiology, The University of Hong Kong, Hong Kong, China.
authors.forename: Haobo
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Anesthesiology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Chaojin
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Yihan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Anaesthesiology, The University of Hong Kong, Hong Kong, China.
authors.forename: Wai Lydia
authors.initials: WL
authors.lastname: Tai
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China.|Department of Anaesthesiology, The University of Hong Kong, Hong Kong, China.
authors.forename: Zhengyuan
authors.initials: Z
authors.lastname: Xia
authors.affiliation: Department of Anesthesiology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Ziqing
authors.identifier: 0000-0002-0649-0624
authors.initials: Z
authors.lastname: Hei
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D000073939:Dysferlin / Q000235:genetics / Q000378:metabolism*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000378:metabolism / Q000494:pharmacology; D034622:RNA Interference; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000073939:Dysferlin; D009124:Muscle Proteins; D020011:Protective Agents; D011994:Recombinant Proteins; C000604080:TRIM72 protein, rat; D033921:Vesicular Transport Proteins
keywords: dysferlin; hepatic ischaemia/reperfusion; mitsugumin-53; reactive oxygen species