| First Author | Aguiar CJ | Year | 2014 |
| Journal | Cell Commun Signal | Volume | 12 |
| Pages | 78 | PubMed ID | 25539979 |
| Mgi Jnum | J:308096 | Mgi Id | MGI:6725966 |
| Doi | 10.1186/s12964-014-0078-2 | Citation | Aguiar CJ, et al. (2014) Succinate causes pathological cardiomyocyte hypertrophy through GPR91 activation. Cell Commun Signal 12:78 |
| abstractText | 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 IIdelta (CaMKIIdelta) 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. 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. |
