Open AccessDownregulation of β-Adrenoceptors in Isoproterenol-Induced Cardiac Remodeling through HuR
Author(s) -
Qian Yin,
Chengzhi Yang,
Jimin Wu,
Haiyan Lu,
Xiaohui Zheng,
Youyi Zhang,
Zhizhen Lv,
Xuemei Zheng,
Zijian Li
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0152005
Subject(s) - creb , downregulation and upregulation , ventricular remodeling , messenger rna , untranslated region , three prime untranslated region , transcription factor , microbiology and biotechnology , receptor , chemistry , medicine , biology , heart failure , endocrinology , gene , biochemistry
β-adrenergic receptors (β-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 β-AR expression in remodeling hearts is still unclear. This study aims to clarify the possible mechanisms underlying the regulation of β 1 - and β 2 -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 mg·kg −1 ·d −1 for 7days. We found that the expression of β 1 - and β 2 -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.