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.
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