Succinate modulates Ca2+ transient and cardiomyocyte viability through PKA-dependent pathway

被引：58
作者：
Aguiar, Carla J. [1 ]
Andrade, Vanessa L. [1 ]
Gomes, Eneas R. M. [1 ]
Alves, Marcia N. M. [1 ]
Ladeira, Marina S. [1 ]
Pinheiro, Ana Cristina N. [1 ]
Gomes, Dawidson A. [2 ]
Almeida, Alvair P. [1 ]
Goes, Alfredo M. [2 ]
Resende, Rodrigo R. [3 ]
Guatimosim, Silvia [1 ]
Leite, M. Fatima [1 ,4 ]
机构：
[1] Univ Fed Minas Gerais, Dept Physiol & Biophys, BR-31270901 Belo Horizonte, MG, Brazil
[2] Univ Fed Minas Gerais, Dept Biochem & Immunol, BR-31270901 Belo Horizonte, MG, Brazil
[3] Univ Fed Minas Gerais, Dept Phys, BR-31270901 Belo Horizonte, MG, Brazil
[4] Howard Hughes Med Inst, Chevy Chase, MD USA
来源：
CELL CALCIUM | 2010年 / 47卷 / 01期
关键词：
Succinate; Cardiomyocytes; Calcium; PKA; DICARBOXYLATE TRANSPORTER; FUNCTIONAL-CHARACTERIZATION; RECEPTOR GPR91; HEART-FAILURE; RAT; APOPTOSIS; LIVER; PHOSPHORYLATION; REPERFUSION; ACID;
D O I：
10.1016/j.ceca.2009.11.003
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
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 Ca2+ transient, by increasing the phosphorylation levels of ryanodine receptor and phospholamban, two well known Ca2+ handling proteins. The effects of succinate on Ca2+ 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 Ca2+ transient and cell viability through a PKA-dependent pathway. (C) 2009 Elsevier Ltd. All rights reserved.
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收藏
页码：37 / 46
页数：10
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