解放军医学杂志2017，Vol.42Issue(12)：1051-1055,5.DOI:10.11855/j.issn.0577-7402.2017.12.05
线粒体钙离子摄入蛋白1在血管紧张素Ⅱ诱导小鼠心肌肥大病理变化中的保护作用
Protection of MICU1 against myocardial hypertrophy induced by angiotensin Ⅱ
摘要
Abstract
Objective To investigate the role of mitochondrial calcium uptake 1 (MICUI) in myocardial hypertrophy of mice and underlying mechanism.Methods The model of myocardial hypertrophy was established via incubation of mouse cardiac myocytes (MCM) with 300nmol/L angiotensin Ⅱ (Ang Ⅱ) for 48 hours in vitro.After that,MICU1 specific small interfering RNA (siRNA) was delivered to knockdown MICU1 levels in MCM.On the other hand,adenovirus-mediated over-expression of MICU 1 was transfected into MCM.Accordingly,the expressions of ANP and BNP in myocardial cells were measured by qRT-PCR.Mitochondrial membrane potential and ATP contents were detected byJC-1 assay kit and ATP assay kit,respectively.Then,Western blotting and qRT-PCR were used to detect the levels of MICU1 in myocardial cells.The mitochondrial Ca2+ contents were measured via atomic absorption flame spectroscopy.The size of myocardial cells was determined by α-actinin staining.Results Mitochondrial membrane potential and ATP contents in hypertrophic cardiomyocytes induced by Ang Ⅱ were both decreased.Meanwhile,myocardial hypertrophy significantly increased mitochondrial Ca2+ contents but decreased MICU1 levels.With the method of genetic intervention,we found that MICUI deficiency exacerbated mitochondrial Ca2+ overload,increased cell surface and elevated the expression of BNP.Conversely,the overexpression of MICU1 obviously decreased mitochondrial Ca2+ overload,cell surface of MCM and expressions of ANP and BNP.Conclusion MICU1 alleviates Ang Ⅱ-induced myocardial hypertrophy via inhibiting mitochondrial Ca2+ overload.关键词
心肌肥大/线粒体钙离子摄入蛋白1/线粒体/钙超载Key words
myocardial hypertrophy/mitochondrial calcium uptake 1/mitochondrial/Ca2+ overload分类
医药卫生引用本文复制引用
杨怡,田玥,沈阳,关美丽,陈莎,冯健,裴海峰,杨永健..线粒体钙离子摄入蛋白1在血管紧张素Ⅱ诱导小鼠心肌肥大病理变化中的保护作用[J].解放军医学杂志,2017,42(12):1051-1055,5.基金项目
国家自然科学基金(81500208) （81500208）
中国博士后基金(2017M613429) （2017M613429）
四川省杰出青年基金(2017JQ0012) （2017JQ0012）
成都军区总医院博士后医院管理基金(41732BA) （41732BA）
This work was supported by the National Natural Science Foundation of China (81500208),China Postdoctoral Science Foundation (2017M613429),the Science Funding for Distinguish Young Scholars of Sichuan Province (2017JQ0012),and the Postdoctoral Startup Funds of Chengdu Military General Hospital (41732BA) （81500208）
