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Succinate causes pathological cardiomyocyte hypertrophy through GPR91 activation.
- Source :
- Cell Communication & Signaling; 2014, Vol. 12 Issue 1, p58-89, 32p
- Publication Year :
- 2014
-
Abstract
- Background: Succinate 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. Results: We 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 IId (CaMKIId) and the translocation of histone deacetylase 5 (HDAC5) into the cytoplasm, which are hypertrophicsignaling events. Furthermore, we found that serum levels of succinate are increased in patients with cardiac hypertrophy associated with acute and chronic ischemic diseases. Conclusions: These 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 1478811X
- Volume :
- 12
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Cell Communication & Signaling
- Publication Type :
- Academic Journal
- Accession number :
- 100416154
- Full Text :
- https://doi.org/10.1186/s12964-014-0078-2