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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.)

Beta-arrestin 2 mediates cardiac hypertrophy induced by thyroid hormones via AT1R

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Author(s):
Lino, Caroline Antunes [1] ; de Bortoli Teixeira, Larissa [2] ; Capelupe Simoes, Sarah [2] ; de Oliveira Silva, Tabatha [1] ; Diniz, Gabriela Placona [1] ; da Costa-Neto, Claudio Miguel [2] ; Barreto-Chaves, Maria Luiza Morais [1]
Total Authors: 7
Affiliation:
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, Sao Paulo - Brazil
[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem & Immunol, Sao Paulo - Brazil
Total Affiliations: 2
Document type: Journal article
Source: Journal of Cellular Physiology; v. 236, n. 6 DEC 2020.
Web of Science Citations: 0
Abstract

We have previously reported that angiotensin II receptor type 1 (AT1R) contributes to the hypertrophic effects of thyroid hormones (TH) in cardiac cells. Even though evidence indicates crosstalks between TH and AT1R, the underlying mechanisms are poorly understood. Beta-arrestin (ARRB) signaling has been described as noncanonical signal transduction pathway that exerts important effects in the cardiovascular system through G-protein-coupled receptors, as AT1R. Herein, we investigated the contribution of ARRB signaling in TH-induced cardiomyocyte hypertrophy. Primary cardiomyocyte cultures were treated with Triiodothyronine (T3) to induce cell hypertrophy. T3 rapidly activates extracellular signal-regulated kinase 1/2 (ERK1/2) signaling, which was partially inhibited by AT1R blockade. Also, ERK1/2 inhibition attenuated the hypertrophic effects of T3. ARRB2 was upregulated by T3, and small interfering RNA assays revealed the role of ARRB2-but not ARRB1-on ERK1/2 activation and cardiomyocyte hypertrophy. Corroborating these findings, the ARRB2-overexpressed cells showed increased expression of hypertrophic markers, which were attenuated by ERK1/2 inhibition. Immunocytochemistry and immunoprecipitation assays revealed the increased expression of nuclear AT1R after T3 stimulation and the increased interaction of AT1R/ARRB2. The inhibition of endocytosis also attenuated the T3 effects on cardiac cells. Our results evidence the contribution of ARRB2 on ERK1/2 activation and cardiomyocyte hypertrophy induced by T3 via AT1R. (AU)

FAPESP's process: 16/13896-0 - AT1R internalization and Ras/Raf/MEK/ERK signaling in the cardiomyocyte hypertrophy induced by thyroid hormone. role of beta-arrestins
Grantee:Maria Luiza de Morais Barreto de Chaves
Support type: Regular Research Grants
FAPESP's process: 13/16142-9 - THYROID HORMONE EFFECT IN ANGIOTENSIN II TYPE 1 RECEPTOR (AT1R) INTERNALIZATION AND ACTIVATION OF Ras/Raf/MEK/ERK IN CARDIOMYOCYTE HYPERTROPHY. BETA-ARRESTINS INVOLVEMENT.
Grantee:Caroline Antunes Lino
Support type: Scholarships in Brazil - Doctorate