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SUCCINATE CAUSES CARDIOMYOCYTE HYPERTROPHY THROUGH GPR91 ACTIVATION

Aguiar, Carla J and Rocha-Franco, Joao A and Souza, Pedro A and Santos, Anderson K and Ladeira, Marina and Rocha-Resende, Cibele and Ladeira, Luis O and Resende, Rodrigo R and Botoni, Fernando A and Barrouin Melo, Marcos and Lima, Cristiano X and Carballido, Jose and Cunha, Thiago M and Menezes, Gustavo B and Guatimosim, Silvia and Leite, M Fatima (2014) SUCCINATE CAUSES CARDIOMYOCYTE HYPERTROPHY THROUGH GPR91 ACTIVATION. Cell Communication and Signaling.

Abstract

SBackgroundSuccinate is an intermediate of the citric acid cycle as well as an extracellular circulating molecule, whose receptor, G protein-coupled receptor-91 (GPR91), was recently identified and characterized in several tissues, including heart. Because some pathological conditions such as ischemia increase succinate blood levels, we investigated the role of this metabolite during a heart ischemic event, using human and rodent models.ResultsWe found that succinate causes cardiac hypertrophy in a GPR91 dependent manner. GPR91 activation triggers the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), the expression of calcium/calmodulin dependent protein kinase II¿ (CaMKII¿) and the translocation of histone deacetylase 5 (HDAC5) into the cytoplasm, which are hypertrophic-signaling events. Furthermore, we found that serum levels of succinate are increased in patients with cardiac hypertrophy associated with acute and chronic ischemic diseases.ConclusionsThese results show for the first time that succinate plays an important role in cardiomyocyte hypertrophy through GPR91 activation, and extend our understanding of how ischemia can induce hypertrophic cardiomyopathy.

Item Type: Article
Keywords: GPR91
Date Deposited: 13 Oct 2015 13:13
Last Modified: 13 Oct 2015 13:13
URI: https://oak.novartis.com/id/eprint/21602

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