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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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]
Total Authors: 6
Affiliation:
[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
Total Affiliations: 2
Document type: Journal article
Source: JOURNAL OF MOLECULAR ENDOCRINOLOGY; v. 49, n. 1, p. 11-20, AUG 2012.
Web of Science Citations: 8
Abstract

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)

FAPESP's process: 06/61523-7 - Cellular and molecular aspects of muscular plasticity
Grantee:Anselmo Sigari Moriscot
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 08/01489-5 - Evaluation of the renin-angiotensin system in adult offspring in response to alterations during the perinatal period
Grantee:Joel Claudio Heimann
Support Opportunities: Research Projects - Thematic Grants