Myofibrillogenesis regulator-1 attenuates hypoxia/reoxygenation-induced injury by repairing microfilaments in neonatal rat cardiomyocytes.
Myofibrillogenesis regulator-1 attenuates hypoxia/reoxygenation-induced injury by repairing microfilaments in neonatal rat cardiomyocytes.
复制标题
肌原纤维生成调节剂-1 通过修复新生大鼠心肌细胞中的微丝来减轻缺氧/复氧引起的损伤。
DOI：
10.1016/j.yexcr.2015.05.026
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发表时间：
2015-10
影响因子：
3.7
通讯作者：
Liu Xh
中科院分区：
文献类型：
--
作者：
Tao T Liu M,;Wang XR;Liu M;Liu Xh
缺氧/再氧化（H/R）损伤以心肌细胞微丝重组为特征。既往研究表明，肌原纤维生成调节因子-1 （MR-1）在心肌中表达，促进心肌细胞中肌动蛋白的组织。本研究旨在探讨MR-1通过促进微丝的修复，在心肌细胞缺氧/再氧化损伤中的作用。为了解决这一问题，采用培养的新生儿心肌细胞H/R模型，通过免疫荧光显微镜分析丝状肌动蛋白（F-actin）和α-actin组织。RT-PCR检测MR-1和肌球蛋白调节轻链-2 (MLC-2) mRNA水平。Western blot检测MR-1和丝状肌动蛋白/球状肌动蛋白（F-/G-actin）蛋白水平，MLC-2和肌球蛋白轻链激酶（MLCK）磷酸化和蛋白表达。我们还探讨了过表达或敲低MR-1对H/R损伤和MLCK/MLC-2/F-actin通路的影响。我们发现，与对照组相比，H/R诱导心肌细胞损伤和F-肌动蛋白和α-肌动蛋白的破坏，F-/ g -肌动蛋白比值降低。与H/R组相比，MR-1过表达减轻H/R诱导的心肌细胞F-肌动蛋白和α-肌动蛋白的损伤和破坏，F-/ g -肌动蛋白比值升高。MR-1过表达也上调了H/ r诱导的MLCK和MLC-2磷酸化。然而，MR-1敲低会进一步破坏F-肌动蛋白和α-肌动蛋白，并降低F-/ g -肌动蛋白比值，从而加重H/R损伤。MR-1敲低还可下调H/R损伤诱导的MLCK和MLC-2磷酸化。这些发现表明MR-1通过激活MLCK/MLC-2通路促进微丝重组，从而减轻H/ r诱导的心肌细胞损伤。
Hypoxia/reoxygenation (H/R) injury is characterized by microfilament reorganization in cardiomyocytes. Previous studies have shown that myofibrillogenesis regulator-1 (MR-1) is expressed in the myocardium and promotes actin organization in cardiomyocytes. The purpose of this study was to investigate the role of MR-1 in attenuating hypoxia/reoxygenation injury in cardiomyocytes through promoting restoration of the microfilament. To address this aim, an H/R model of cultured neonatal cardiomyocytes was used to assess filamentous actin (F-actin) and α-actinin organization through immunofluorescence microscopy analysis. RT-PCR was used to detect mRNA levels of MR-1 and myosin regulatory light chain-2 (MLC-2). Western blot analysis was used to detect protein levels of MR-1 and filamentous actin/globular actin (F-/G-actin) as well as MLC-2 and myosin light chain kinase (MLCK) phosphorylation and protein expression. We also explored the effects of overexpressing or knocking down MR-1 on H/R injury and the MLCK/MLC-2/F-actin pathway. We found that H/R induced cardiomyocyte injury and disruption of F-actin and α-actinin with a decrease in the F-/G-actin ratio compared with controls. Compared with the H/R group, MR-1 overexpression attenuated H/R-induced injury and disruption of F-actin and α-actinin in cardiomyocytes with an increase in the F-/G-actin ratio. MR-1 overexpression also up-regulated H/R-induced MLCK and MLC-2 phosphorylation. However, MR-1 knockdown aggravated H/R injury by further disrupting F-actin and α-actinin, as well as decreasing the F-/G-actin ratio. MR-1 knockdown also down-regulated MLCK and MLC-2 phosphorylation induced by H/R injury. These findings suggest that MR-1 attenuates H/R-induced cardiomyocyte injury by promoting microfilament reorganization through the activation of the MLCK/MLC-2 pathway.
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影响因子：
15.9
作者：
Sheikh, Farah;Ouyang, Kunfu;Chen, Ju
通讯作者：
Chen, Ju
影响因子：
37.8
作者：
Warren SA;Briggs LE;Zeng H;Chuang J;Chang EI;Terada R;Li M;Swanson MS;Lecker SH;Willis MS;Spinale FG;Maupin-Furlowe J;McMullen JR;Moss RL;Kasahara H
通讯作者：
Kasahara H
DOI：
10.1042/bj2090635
发表时间：
1983-03
期刊：
The Biochemical journal
影响因子：
--
作者：
M. Reddy;M. Rabinowitz;R. Zak
通讯作者：
M. Reddy;M. Rabinowitz;R. Zak
影响因子：
3.5
作者：
Gong, Yuyan;He, Hongwei;Shao, Rong-Guang
通讯作者：
Shao, Rong-Guang
肌原纤维生成调节因子 1 保护肾脏免受缺血/再灌注损伤
影响因子：
4.2
作者：
Wang, Xiaoreng;Tao, Tianqi;Liu, Xiuhua
通讯作者：
Liu, Xiuhua