THE UBIQUITIN PROTEASOME SYSTEM IN CARDIAC HYPERTROPHY MODEL INDUCED BY THYROID HORMONES.

Abstract

Due to their high level of differentiation, the cardiac muscle cells are not able to undergo the cell division process. In this sense, the cardiomyocytes developed mechanisms of adaptation in response to changes in the homeostasis of cardiac tissue, being the regulation of the cell size the main mechanism of cytoprotection for this cell type. Intracellular signaling pathways associated to regulation of cell size, survival and death are controlled by protein basal levels, which result from the balance between protein synthesis and degradation. The Ubiquitin Proteasome System (UPS) represents the main mechanism of intracellular proteolysis in eukaryotic cells and emerging evidences suggest the involvement of this system in the pathogenesis of some cardiac diseases, like in cardiac hypertrophy. The activation of this system was demonstrated in distinct models of cardiac hypertrophy and was evidenced by the increase in the number of ubiquitinated proteins, upregulation of catalytic proteasome subunits and increase in the proteolytic activity of proteasome. In addition, the inhibition of UPS is known to prevent the increase of cardiac mass and its integrity is essential for the maintenance of compensated cardiac hypertrophy. Thyroid hormones present classical actions in the cardiovascular system and interfere in the regulation of multiples signaling pathways, which modulate the cardiac trophysm. Therefore, the objective of the present study is to evaluate the participation of UPS in the thyroid hormone-induced cardiac hypertrophy in vivo and in vitro.