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

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]

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

• 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
• Modalidade de apoio: 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
• Modalidade de apoio: Bolsas no Brasil - Doutorado