Tbx20 functions as an important regulator of estrogen-mediated cardiomyocyte protection during oxidative stress
Tbx20 functions as an important regulator of estrogen-mediated cardiomyocyte protection during oxidative stress
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Tbx20 在氧化应激过程中充当雌激素介导的心肌细胞保护的重要调节剂。
DOI：
10.1016/j.ijcard.2013.06.018
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发表时间：
2013-10-09
影响因子：
3.5
通讯作者：
Li, Jian
中科院分区：
文献类型：
--
作者：
Shen, Tao;Yang, Chongqing;Li, Jian
背景资料：T-box 20（Tbx 20）是一种主要在心血管系统表达的转录因子，在胚胎心血管系统发育和成年心脏功能中起重要作用。在这里，我们确定的机制，Tbx 20调节心肌细胞凋亡和cardiomyopathies.Methods：我们分析了Tbx 20的表达水平和凋亡率在正常和心力衰竭的人尸检心脏样本。切除雌性C57 BL/6小鼠的卵巢并用17 β-雌二醇处理以测定Tbx 20表达水平。对雄性C57 BL/6横向主动脉缩窄诱导的心力衰竭样品和用H2 O2处理的新生大鼠心室肌细胞进行ROS产生、TUNEL、DNA梯状、qRT-PCR、Western印迹、免疫组织化学和ChIP分析，以研究Tbx 20在雌激素介导的心脏保护中的作用。Tbx 20表达在心力衰竭期间下调，伴随着人类和小鼠心肌细胞凋亡水平升高。H2 O2导致Tbx 20表达的同时减少，并在培养的新生大鼠心肌细胞的凋亡增加。Tbx 20过表达减少H2 O2诱导的心肌细胞凋亡，并与p38 MAPK，Bax和caspase 3的抑制和Bcl-2的激活有关。雌激素能够保护心肌细胞免受H2 O2诱导的凋亡，上调Tbx 20表达的浓度依赖性方式。Tbx 20沉默增加H9 c2细胞中氧化应激诱导的凋亡。此外，Tbx 20直接调节Esrra的表达，以提高心脏的保护作用，estrogen.Conclusions：这些结果表明，Tbx 20功能作为一个重要的调节器，雌激素介导的心肌细胞保护氧化应激过程中，这表明雌激素-Tbx 20-ERR-a可能代表一个重要的监管级联反应和潜在的治疗目标，为心力衰竭。皇冠版权所有（C）2013由爱思唯尔爱尔兰有限公司出版。保留所有权利。
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.