| Literature DB >> 20018372 |
Carla J Aguiar1, Vanessa L Andrade, Enéas R M Gomes, Márcia N M Alves, Marina S Ladeira, Ana Cristina N Pinheiro, Dawidson A Gomes, Alvair P Almeida, Alfredo M Goes, Rodrigo R Resende, Silvia Guatimosim, M Fatima Leite.
Abstract
GPR91 is an orphan G-protein-coupled receptor (GPCR) that has been characterized as a receptor for succinate, a citric acid cycle intermediate, in several tissues. In the heart, the role of succinate is unknown. We now report that rat ventricular cardiomyocytes express GPR91. We found that succinate, through GPR91, increases the amplitude and the rate of decline of global Ca(2+) transient, by increasing the phosphorylation levels of ryanodine receptor and phospholamban, two well known Ca(2+) handling proteins. The effects of succinate on Ca(2+) transient were abolished by pre-treatment with adenylyl cyclase and cAMP-dependent protein kinase (PKA) inhibitors. Direct PKA activation by succinate was further confirmed using a FRET-based A-kinase activity reporter. Additionally, succinate decreases cardiomyocyte viability through a caspase-3 activation pathway, effect also prevented by PKA inhibition. Taken together, these observations show that succinate acts as a signaling molecule in cardiomyocytes, modulating global Ca(2+) transient and cell viability through a PKA-dependent pathway. 2009 Elsevier Ltd. All rights reserved.Entities:
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Year: 2009 PMID： 20018372 DOI： 10.1016/j.ceca.2009.11.003
Source DB: PubMed Journal: Cell Calcium ISSN： 0143-4160 Impact factor: 6.817