Protection of MICU1 against myocardial hypertrophy induced by angiotensin Ⅱ
10.11855/j.issn.0577-7402.2017.12.05
- VernacularTitle: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
- Author:
Yi YANG
1
;
Yue TIAN
;
Yang SHEN
;
Mei-Li GUAN
;
Sha CHEN
;
Jian FENG
;
Hai-Feng PEI
;
Yong-Jian YANG
Author Information
1. 646000,四川泸州 西南医科大学临床医学院
- Keywords:
myocardial hypertrophy;
mitochondrial calcium uptake 1;
mitochondrial;
Ca2+ overload
- From:
Medical Journal of Chinese People's Liberation Army
2017;42(12):1051-1055
- CountryChina
- Language:Chinese
-
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.
