title: Tbx20 functions as an important regulator of estrogen-mediated cardiomyocyte protection during oxidative stress.
abstract: BACKGROUND
  As a transcription factor mainly expressed in cardiovascular system, T-box 20 (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 17β-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-α may represent a crucial regulatory cascade and a potential therapeutic target for heart failure.
authors.affiliation: Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Shen
authors.forename: Chongqing
authors.initials: C
authors.lastname: Yang
authors.forename: Ling
authors.initials: L
authors.lastname: Ding
authors.forename: Yuping
authors.initials: Y
authors.lastname: Zhu
authors.forename: Yang
authors.initials: Y
authors.lastname: Ruan
authors.forename: Hongqiang
authors.initials: H
authors.lastname: Cheng
authors.forename: Weiwei
authors.initials: W
authors.lastname: Qin
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Huang
authors.forename: Hangxiang
authors.initials: H
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Man
authors.forename: Dongge
authors.initials: D
authors.lastname: Liu
authors.forename: Shu
authors.initials: S
authors.lastname: Wang
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Bian
authors.forename: Chuanshi
authors.initials: C
authors.lastname: Xiao
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Jian
authors.initials: J
authors.lastname: Li
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004967:Estrogens / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020825:T-Box Domain Proteins / Q000096:biosynthesis*
chemical_list: D004967:Estrogens; D020825:T-Box Domain Proteins; C420984:TBX20 protein, human
keywords: 17β-estradiol; Apoptosis; Esrra; Heart failure; Oxidative stress; Tbx20