THYROID HORMONE EFFECT IN ANGIOTENSIN II TYPE 1 RECEPTOR (AT1R) INTERNALIZATION AND ACTIVATION OF Ras/Raf/MEK/ERK IN CARDIOMYOCYTE HYPERTROPHY. BETA-ARRESTINS INVOLVEMENT.

• Grant number: 13/16142-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: December 01, 2013
• End date: July 31, 2017
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Maria Luiza de Morais Barreto de Chaves
• Grantee: Caroline Antunes Lino
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

In order to better understand the previously described interaction between the renin angiotensin system (RAS), specifically the angiotensin II receptor type 1 (AT1R), and the effects of thyroid hormone (T3) administration in cardiac muscle cells, this study proposes the analysis of receptor internalization - an important mechanism of signal transduction regulation. The ²-arrestins (²ARRs) are multifunctional proteins involved in the regulation of G-protein coupled receptors (GPCRs) through mechanisms of desensitization and internalization. It is known that ²ARRs as scaffold proteins may interact with various intracellular proteins and promote the internalization of GPCRs through endosome vesicles potentially related to signal transduction. It is a non-canonical signal transduction pathway that is independent of G protein activation. Components of mitogen-activated protein kinases (MAPKs), such as ERK ½, when associated with these vesicles promote the regulation of cytosolic downstream effectors. The biological difference from the activation of G protein-dependent and independent signaling has not been established. The aim of this study is to evaluate the effects of T3 on AT1R internalization and activation of Ras/Raf/MEK/ERK signaling to cardiomyocyte hypertrophy. This study is strongly supported since we have previously described the important contribution of AT1R in cardiomyocyte hypertrophy induced by T3 although the molecular mechanisms associated are still poorly understood.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

LINO, CAROLINE ANTUNES; MORAIS BARRETO-CHAVES, MARIA LUIZA. Contribution of Beta-Arrestin Signaling on Thyroid Hormone-Induced Cardiac Hypertrophy. FASEB JOURNAL, v. 31, p. 1-pg., 2017-04-01. (16/13896-0, 13/16142-9)

LINO, CAROLINE ANTUNES; BARRETO-CHAVES, MARIA LUIZA. Beta-arrestins in the context of cardiovascular diseases: Focusing on angiotensin II type 1 receptor (AT1R). CELLULAR SIGNALLING, v. 92, p. 9-pg., 2022-02-01. (13/16142-9, 16/13896-0)

LINO, CAROLINE ANTUNES; DE BORTOLI TEIXEIRA, LARISSA; CAPELUPE SIMOES, SARAH; DE OLIVEIRA SILVA, TABATHA; DINIZ, GABRIELA PLACONA; DA COSTA-NETO, CLAUDIO MIGUEL; BARRETO-CHAVES, MARIA LUIZA MORAIS. Beta-arrestin 2 mediates cardiac hypertrophy induced by thyroid hormones via AT1R. Journal of Cellular Physiology, v. 236, n. 6, DEC 2020. (16/13896-0, 13/16142-9)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

LINO, Caroline Antunes. Contribution of beta-arrestin signaling mediated by angiotensin II receptor type 1 in cardiomyocyte hypertrophy induced by T3.. 2018. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.