New insight into the mechanisms associated with the rapid effect of T-3 on AT1R expression


Autoria(s): Diniz, Gabriela Placoná; Cremasco Takano, Ana Paula; Bruneto, Erika; Silva, Francemilson Goulart da; Nunes, Maria Tereza; Chaves, Maria Luiza Morais Barreto de
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

05/11/2013

05/11/2013

2012

Resumo

The angiotensin II type 1 receptor (AT1R) is involved in the development of cardiac hypertrophy promoted by thyroid hormone. Recently, we demonstrated that triiodothyronine (T-3) rapidly increases AT1R mRNA and protein levels in cardiomyocyte cultures. However, the molecular mechanisms responsible for these rapid events are not yet known. In this study, we investigated the T-3 effect on AT1R mRNA polyadenylation in cultured cardiomyocytes as well as on the expression of microRNA-350 (miR-350), which targets AT1R mRNA. The transcriptional and translational actions mediated by T-3 on AT1R levels were also assessed. The total content of ubiquitinated proteins in cardiomyocytes treated with T-3 was investigated. Our data confirmed that T-3 rapidly raised AT1R mRNA and protein levels, as assessed by real-time PCR and western blotting respectively. The use of inhibitors of mRNA and protein synthesis prevented the rapid increase in AT1R protein levels mediated by T-3. In addition, T-3 rapidly increased the poly-A tail length of the AT1R mRNA, as determined by rapid amplification of cDNA ends poly-A test, and decreased the content of ubiquitinated proteins in cardiomyocytes. On the other hand, T-3 treatment increased miR-350 expression. In parallel with its transcriptional and translational effects on the AT1R, T-3 exerted a rapid posttranscriptional action on AT1R mRNA polyadenylation, which might be contributing to increase transcript stability, as well as on translational efficiency, resulting to the rapid increase in AT1R mRNA expression and protein levels. Finally, these results show, for the first time, that T-3 rapidly triggers distinct mechanisms, which might contribute to the regulation of AT1R levels in cardiomyocytes. Journal of Molecular Endocrinology (2012) 49, 11-20

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Foundation for the Support of Research in the State of Sao Paulo) [06/61523-7, 08/01489-5]

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Foundation for the Support of Research in the State of Sao Paulo)

Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq, National Council for Scientific and Technological Development)

Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq, National Council for Scientific and Technological Development)

Identificador

JOURNAL OF MOLECULAR ENDOCRINOLOGY, BRISTOL, v. 49, n. 1, supl. 1, Part 1, pp. 11-20, AUG, 2012

0952-5041

http://www.producao.usp.br/handle/BDPI/41933

10.1530/JME-11-0141

http://dx.doi.org/10.1530/JME-11-0141

Idioma(s)

eng

Publicador

BIOSCIENTIFICA LTD

BRISTOL

Relação

JOURNAL OF MOLECULAR ENDOCRINOLOGY

Direitos

restrictedAccess

Copyright BIOSCIENTIFICA LTD

Palavras-Chave #UBIQUITIN-PROTEASOME SYSTEM #RENIN-ANGIOTENSIN SYSTEM #MESSENGER-RNA STABILITY #THYROID-HORMONE ACTION #CARDIAC-HYPERTROPHY #POSTTRANSCRIPTIONAL REGULATION #GENE-EXPRESSION #RECEPTOR EXPRESSION #NONGENOMIC ACTIONS #HEART-FAILURE #ENDOCRINOLOGY & METABOLISM
Tipo

article

original article

publishedVersion