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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.)

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

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Autor(es):
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]
Número total de Autores: 7
Afiliação do(s) autor(es):
[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
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: Journal of Cellular Physiology; v. 236, n. 6 DEC 2020.
Citações Web of Science: 0
Resumo

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)

Processo FAPESP: 16/13896-0 - Internalização do receptor de Ang II (AT1R) e ativação da sinalização Ras/Raf/MEK/ERK no estabelecimento da hipertrofia cardiomiocítica induzida por hormônios tiroideanos - envolvimento das beta-arrestinas
Beneficiário:Maria Luiza de Morais Barreto de Chaves
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 13/16142-9 - EFEITO DO HORMÔNIO TIREOIDIANO NA INTERNALIZAÇÃO DO RECEPTOR DE ANGIOTENSINA II DO TIPO I (AT1R) E ATIVAÇÃO DA SINALIZAÇÃO Ras/Raf/MEK/ERK NO ESTABELECIMENTO DA HIPERTROFIA CARDIOMIOCÍTICA. ENVOLVIMENTO DAS BETA-ARRESTINAS.
Beneficiário:Caroline Antunes Lino
Linha de fomento: Bolsas no Brasil - Doutorado