MG53 anchored by dysferlin to cell membrane reduces hepatocyte apoptosis which induced by ischaemia/reperfusion injury in vivo and in vitro.
MG53 anchored by dysferlin to cell membrane reduces hepatocyte apoptosis which induced by ischaemia/reperfusion injury in vivo and in vitro.
复制标题
MG53通过dysferlin锚定在细胞膜上减少体内和体外缺血/再灌注损伤诱导的肝细胞凋亡
DOI：
10.1111/jcmm.13171
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发表时间：
2017-10
影响因子：
5.3
通讯作者：
Hei Z
中科院分区：
文献类型：
--
作者：
Yao W;Li H;Han X;Chen C;Zhang Y;Tai WL;Xia Z;Hei Z
肝缺血再灌注（Hepatic ischaemia/reperfusion，HIR）可引起肝细胞膜严重损伤，导致肝细胞死亡和HIR损伤。在这项研究中，我们研究了Mitsugumin-53（MG 53），一种新的细胞膜修复蛋白，在保护肝脏免受HIR损伤中的作用和机制。对大鼠进行假手术或在诱导HIR前2小时尾静脉注射重组MG 53（rhMG 53）或不注射重组MG 53（rhMG 53）的70%温热HIR。在体外，培养的肝细胞AML 12细胞在rhMG 53和/或dysferlin基因shRNA或腺病毒转染的存在下经受缺氧/复氧（H/R）。HIR导致严重的肝损伤，表现为严重的肝组织学改变和AST、ALT释放增加。缺血后肝脏氧化应激显著增强，表现为二氢乙锭水平升高、4-羟基壬烯醛增加、15-F2 t-异前列烷增加和SOD活性降低。rhMG 53给药减轻了HIR后肝损伤，降低了肝氧化应激，并进一步增强了dysferlin蛋白表达及其与MG 53的共定位。类似地，H/R诱导AML 12细胞损伤和氧化应激，其被rhMG 53或dysferlin过表达所消除，但被dysferlin基因敲除所加剧。Dysferlin过表达进一步增加H/R诱导的MG 53和dysferlin共定位增加。总之，MG 53被dysferlin锚定以减少氧化应激和细胞死亡并减弱HIR损伤。
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.
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DOI：
10.1038/nri2413
发表时间：
2008-11
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Ozato K;Shin DM;Chang TH;Morse HC 3rd
通讯作者：
Morse HC 3rd
DOI：
10.1016/b978-0-12-394309-5.00006-7
发表时间：
2012
影响因子：
--
作者：
Kalogeris, Theodore;Baines, Christopher P.;Krenz, Maike;Korthuis, Ronald J.
通讯作者：
Korthuis, Ronald J.
影响因子：
0.7
作者：
Aasen T;Achdjian H;Usta Y;Nanda R
通讯作者：
Nanda R
脂氧素 A4 预处理通过 Keap1/Nrf2 通路以脂氧素 A4 受体独立的方式减轻肠缺血再灌注损伤。
影响因子：
--
作者：
Han X;Yao W;Liu Z;Li H;Zhang ZJ;Hei Z;Xia Z
通讯作者：
Xia Z
影响因子：
11.8
作者：
Roostalu, Urmas;Straehle, Uwe
通讯作者：
Straehle, Uwe