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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

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Autor(es):
Diniz, Gabriela Placona [1] ; Cremasco Takano, Ana Paula [1] ; Bruneto, Erika [2] ; da Silva, Francemilson Goulart [2] ; Nunes, Maria Tereza [2] ; Morais Barreto-Chaves, Maria Luiza [1]
Número total de Autores: 6
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Dept Anat, Lab Cellular Biol & Funct Anat, BR-05508900 Sao Paulo - Brazil
[2] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol, BR-05508900 Sao Paulo - Brazil
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: JOURNAL OF MOLECULAR ENDOCRINOLOGY; v. 49, n. 1, p. 11-20, AUG 2012.
Citações Web of Science: 8
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 (AU)

Processo FAPESP: 06/61523-7 - Aspectos celulares e moleculares da plasticidade muscular
Beneficiário:Anselmo Sigari Moriscot
Modalidade de apoio: Auxílio à Pesquisa - Temático
Processo FAPESP: 08/01489-5 - O sistema renina-angiotensina em prole de mães submetidas a alterações no ambiente perinatal
Beneficiário:Joel Claudio Heimann
Modalidade de apoio: Auxílio à Pesquisa - Temático