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EnglishAim: The hypothalamic neuropeptide growth hormone-releasing hormone (GHRH), stimulates growth hormone synthesis and release in the pituitary. GHRH also exerts proliferative effects in extrapituitary cells, whereas GHRH antagonists have been shown to suppress cancer cell proliferation. We investigated GHRH effects on cardiac myocyte cell survival and the underlying signaling mechanisms. Methods and results: RT-PCR analysis showed GHRH-receptor mRNA in adult rat ventricular myocytes (ARVMs) and in rat heart H9c2 cells. In ARVMs, GHRH prevented cell death and caspase-3 activation induced by serum starvation and by the β-adrenergic receptor agonist isoproterenol. The GHRH-R antagonist JV-1-36 abolished GHRH survival action under both experimental conditions. GHRH-induced cardiac cell protection required extracellular signal-regulated kinase (ERK)1/2 and phosphoinositide-3 kinase (PI3K)/Akt activation and adenylyl cyclase/cAMP/protein kinase A signaling. Isoproterenol strongly up-regulated the mRNA and protein of the proapoptotic inducible cAMP early repressor (ICER), whereas GHRH completely blocked this effect. Similarly to ARVMs, in H9c2 cardiac cells GHRH inhibited serum starvation- and isoproterenol-induced cell death and apoptosis through the same signaling pathways. Finally, GHRH improved left ventricular recovery during reperfusion and reduced infarct size in Langendorff-perfused rat hearts, subjected to ischemia-reperfusion injury. These effects involved PI3K/Akt signaling and were inhibited by JV-1-36. Conclusions: Our findings suggest that GHRH promotes cardiac myocyte survival through multiple signaling mechanisms and protects against ischemia/reperfusion injury in isolated rat heart, indicating a novel cardioprotective role of this hormone.
| Titolo: | Ghrh promotes survival of cardiac myocytes in vitro and protects against ischemia-reperfusion injury in rat heart |
| Autori Riconosciuti: | |
| Autori: | Riccarda Granata; Fabio Settanni; Letizia Trovato; Maria Pia Gallo; Silvia Destefanis; Francesca Scarlatti; Alessia Brero; Roberta Ramella; Marco Volante; Jorgen Isgaard; Renzo Levi; Mauro Papotti; Giuseppe Alloatti; Ezio Ghigo |
| Data di pubblicazione: | 2009 |
| Abstract: | Aim: The hypothalamic neuropeptide growth hormone-releasing hormone (GHRH), stimulates growth hormone synthesis and release in the pituitary. GHRH also exerts proliferative effects in extrapituitary cells, whereas GHRH antagonists have been shown to suppress cancer cell proliferation. We investigated GHRH effects on cardiac myocyte cell survival and the underlying signaling mechanisms. Methods and results: RT-PCR analysis showed GHRH-receptor mRNA in adult rat ventricular myocytes (ARVMs) and in rat heart H9c2 cells. In ARVMs, GHRH prevented cell death and caspase-3 activation induced by serum starvation and by the β-adrenergic receptor agonist isoproterenol. The GHRH-R antagonist JV-1-36 abolished GHRH survival action under both experimental conditions. GHRH-induced cardiac cell protection required extracellular signal-regulated kinase (ERK)1/2 and phosphoinositide-3 kinase (PI3K)/Akt activation and adenylyl cyclase/cAMP/protein kinase A signaling. Isoproterenol strongly up-regulated the mRNA and protein of the proapoptotic inducible cAMP early repressor (ICER), whereas GHRH completely blocked this effect. Similarly to ARVMs, in H9c2 cardiac cells GHRH inhibited serum starvation- and isoproterenol-induced cell death and apoptosis through the same signaling pathways. Finally, GHRH improved left ventricular recovery during reperfusion and reduced infarct size in Langendorff-perfused rat hearts, subjected to ischemia-reperfusion injury. These effects involved PI3K/Akt signaling and were inhibited by JV-1-36. Conclusions: Our findings suggest that GHRH promotes cardiac myocyte survival through multiple signaling mechanisms and protects against ischemia/reperfusion injury in isolated rat heart, indicating a novel cardioprotective role of this hormone. |
| Editore: | J Endocrinol Invest "33° Congresso Nazionale della SocietàItaliana di Endocrinologia" Sorrento, 27-30 maggio 2009 |
| Titolo del libro: | J Endocrinol Invest |
| Volume: | - |
| Fascicolo: | - |
| Pagina iniziale: | - |
| Pagina finale: | - |
| Nome del convegno: | Congresso Nazionale della Società Italiana di Endocrinologia |
| Luogo del convegno: | Sorrento, Italia |
| Anno del convegno: | 27-30 maggio 2009 |
| URL: | http://www.jendocrinolinvest.it/jei/it/ |
| Appare nelle tipologie: | 04D-Meeting abstract in volume |
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