Mammalian target of rapamycin is essential for cardiomyocyte survival and heart development in mice

被引:32
作者
Zhang, Pengpeng [1 ,2 ,3 ]
Shan, Tizhong [3 ]
Liang, Xinrong [3 ]
Deng, Changyan [1 ,2 ]
Kuang, Shihuan [3 ]
机构
[1] Huazhong Agr Univ, Coll Anim Sci & Technol, Minist Agr, Key Lab Swine Genet & Breeding, Wuhan 430070, Peoples R China
[2] Huazhong Agr Univ, Coll Anim Sci & Technol, Minisby Educ, Key Lab Agr Anim Genet Breeding & Reprod, Wuhan 430070, Peoples R China
[3] Purdue Univ, Dept Anim Sci, W Lafayette, IN 47907 USA
基金
美国国家卫生研究院;
关键词
mTOR; Heart failure; Cardiomyocyte; CARDIAC-FUNCTION; SKELETAL-MUSCLE; MTOR; GROWTH; PROLIFERATION; EXPRESSION; APOPTOSIS; INHIBITION; METABOLISM; FAILURE;
D O I
10.1016/j.bbrc.2014.08.046
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Mammalian target of rapamycin (mTOR) is a critical regulator of protein synthesis, cell proliferation and energy metabolism. As constitutive knockout of Mtor leads to embryonic lethality, the in vivo function of mTOR in perinatal development and postnatal growth of heart is not well defined. In this study, we established a muscle-specific mTOR conditional knockout mouse model (mTOR-mKO) by crossing MCK-Cre and Mtor(flox/flox) mice. Although the mTOR-mKO mice survived embryonic and perinatal development, they exhibited severe postnatal growth retardation, cardiac muscle pathology and premature death. At the cellular level, the cardiac muscle of mTOR-mKO mice had fewer cardiomyocytes due to apoptosis and necrosis, leading to dilated cardiomyopathy. At the molecular level, the cardiac muscle of mTOR-mKO mice expressed lower levels of fatty acid oxidation and glycolysis related genes compared to the WT littermates. In addition, the mTOR-mKO cardiac muscle had reduced Myh6 but elevated Myh7 expression, indicating cardiac muscle degeneration. Furthermore, deletion of Mtor dramatically decreased the phosphorylation of S6 and AKT, two key targets downstream of mTORC1 and mTORC2 mediating the normal function of mTOR. These results demonstrate that mTOR is essential for cardiomyocyte survival and cardiac muscle function. (C) 2014 Elsevier Inc. All rights reserved.
引用
收藏
页码:53 / 59
页数:7
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