TY - JOUR
T1 - Downregulation of β-adrenoceptors in isoproterenol-induced cardiac remodeling through HuR
AU - Yin, Qian
AU - Yang, Chengzhi
AU - Wu, Jimin
AU - Lu, Haiyan
AU - Zheng, Xiaohui
AU - Zhang, Youyi
AU - Lv, Zhizhen
AU - Zheng, Xiaopu
AU - Li, Zijian
N1 - Publisher Copyright:
© 2016 Yin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/4
Y1 - 2016/4
N2 - β-adrenergic receptors (p-ARs) play an important role in cardiac remodeling, which is the key pathological process in various heart diseases and leads to heart failure. However, the regulation of p-AR expression in remodeling hearts is still unclear. This study aims to clarify the possible mechanisms underlying the regulation of β1- and β2-AR expression in cardiac remodeling. The rat model of cardiac remodeling was established by subcutaneous injection of isoproterenol(ISO) at the dose of 0.25 mgkg-1d-1for 7days. We found that the expression of β1- and β2-ARs decreased in the remodeling heart. The mechanisms may include the inhibition of DNA transcription and the increase of mRNA degradation. cAMP-response element binding protein(CREB) is a well-known transcription factor of β-AR. However, the expression and activation of CREB was not changed in the remodeling heart. Further, human Antigen-R (HuR), a RNA binding protein, which binds to the 3'-untranslated region of the β-AR mRNA and promotes RNA degradation, was increased in the remodeling model. And in vitro, HuR deficiency reversed the reduction of β-AR mRNA induced by ISO. Therefore, the present findings indicate that HuR, but not CREB, is responsible for the reduction of β-AR expression in ISO induced cardiac remodeling.
AB - β-adrenergic receptors (p-ARs) play an important role in cardiac remodeling, which is the key pathological process in various heart diseases and leads to heart failure. However, the regulation of p-AR expression in remodeling hearts is still unclear. This study aims to clarify the possible mechanisms underlying the regulation of β1- and β2-AR expression in cardiac remodeling. The rat model of cardiac remodeling was established by subcutaneous injection of isoproterenol(ISO) at the dose of 0.25 mgkg-1d-1for 7days. We found that the expression of β1- and β2-ARs decreased in the remodeling heart. The mechanisms may include the inhibition of DNA transcription and the increase of mRNA degradation. cAMP-response element binding protein(CREB) is a well-known transcription factor of β-AR. However, the expression and activation of CREB was not changed in the remodeling heart. Further, human Antigen-R (HuR), a RNA binding protein, which binds to the 3'-untranslated region of the β-AR mRNA and promotes RNA degradation, was increased in the remodeling model. And in vitro, HuR deficiency reversed the reduction of β-AR mRNA induced by ISO. Therefore, the present findings indicate that HuR, but not CREB, is responsible for the reduction of β-AR expression in ISO induced cardiac remodeling.
UR - https://www.scopus.com/pages/publications/84963677257
U2 - 10.1371/journal.pone.0152005
DO - 10.1371/journal.pone.0152005
M3 - 文章
C2 - 27035432
AN - SCOPUS:84963677257
SN - 1932-6203
VL - 11
JO - PLoS ONE
JF - PLoS ONE
IS - 4
M1 - e0152005
ER -
