期刊
INTERNATIONAL JOURNAL OF CARDIOLOGY
卷 168, 期 4, 页码 3704-3714出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.ijcard.2013.06.018
关键词
Tbx20; Apoptosis; Heart failure; 17 beta-estradiol; Oxidative stress; Esrra
资金
- National Basic Research Program of China [2012CB517502]
- National Natural Science Foundation of China [81200221, 81070634]
- Scientific Research Foundation for Returned Chinese Scholars of the Ministry of Human Resource and Social Security of the People's Republic of China
Background: As a transcription factor mainly expressed in cardiovascular system, T-box20 (Tbx20) plays an important role in embryonic cardiovascular system development and adult heart function. Here, we determined the mechanism by which Tbx20 regulates cardiomyocyte apoptosis and cardiomyopathies. Methods: We analyzed Tbx20 expression levels and apoptosis rates in normal and heart failure human autopsy heart samples. Female C57BL/6 mice were ovariectomized and treated with 17 beta-estradiol to determine Tbx20 expression levels. ROS production, TUNEL, DNA laddering, qRT-PCR, Western blot, immunohistochemistry and ChIP analyses were performed on male C57BL/6 transverse aortic constriction-induced heart failure samples and on neonatal rat ventricular myocytes that were treated with H2O2 to investigate the role of Tbx20 in estrogen-mediated heart protection. Results: Tbx20 expression was down regulated during heart failure, accompanied by elevated cardiomyocyte apoptotic levels in humans and mice. H2O2 led to a concurrent decrease in Tbx20 expression and increase in apoptosis in cultured neonatal rat cardiomyocytes. Tbx20 overexpression reduced H2O2-induced cardiomyocyte apoptosis and was associated with a profound inhibition of p38MAPK, Bax and caspase3 and the activation of Bcl-2. Estrogen was able to protect cardiomyocytes from H2O2-induced apoptosis by upregulating Tbx20 expression in a concentration-dependent manner. Tbx20 silencing increased oxidative stress-induced apoptosis in H9c2 cells. Moreover, Tbx20 directly regulated Esrra expression to enhance the heart-protective effect of estrogen. Conclusions: These results indicate that Tbx20 functions as an important regulator of estrogen-mediated cardiomyocyte protection during oxidative stress, suggesting that estorgen-Tbx20-ERR-a may represent a crucial regulatory cascade and a potential therapeutic target for heart failure. Crown Copyright (C) 2013 Published by Elsevier Ireland Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据