Growth hormone-releasing hormone promotes survival of cardiac myocytes in vitro and protects against ischaemia-reperfusion injury in rat heart

Autor: Alessia Brero, Letizia Trovato, Francesca Scarlatti, Roberta Ramella, Marco Volante, S. Destefanis, Jörgen Isgaard, Riccarda Granata, Giuseppe Alloatti, Mauro Papotti, Ezio Ghigo, Renzo Levi, Fabio Settanni, Maria Pia Gallo
Rok vydání: 2009
Předmět:
MAPK/ERK pathway
Receptors
Neuropeptide
endocrine system
medicine.medical_specialty
Time Factors
Physiology
Cell Survival
Apoptosis
Myocardial Reperfusion Injury
Biology
Growth Hormone-Releasing Hormone
Ventricular Function
Left
Cell Line
Phosphatidylinositol 3-Kinases
Receptors
Pituitary Hormone-Regulating Hormone
Physiology (medical)
Internal medicine
medicine
Cyclic AMP
Myocyte
Animals
Myocytes
Cardiac
RNA
Messenger
Receptor
Protein kinase A
Protein kinase B
PI3K/AKT/mTOR pathway
Mitogen-Activated Protein Kinase 1
Sermorelin
Mitogen-Activated Protein Kinase 3
Caspase 3
Isoproterenol
Recovery of Function
Adrenergic beta-Agonists
Growth hormone–releasing hormone
Cyclic AMP-Dependent Protein Kinases
Myocardial Contraction
Rats
Perfusion
Endocrinology
Cytoprotection
cardiovascular system
Calcium
Cardiology and Cardiovascular Medicine
hormones
hormone substitutes
and hormone antagonists
medicine.drug
Adenylyl Cyclases
Signal Transduction
Zdroj: Cardiovascular research. 83(2)
ISSN: 1755-3245
Popis: Aims The hypothalamic neuropeptide growth hormone-releasing hormone (GHRH) stimulates GH 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 signalling mechanisms. Methods and results Reverse transcriptase–polymerase chain reaction analysis showed GHRH receptor (GHRH-R) 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 signalling. Isoproterenol strongly upregulated the mRNA and protein of the pro-apoptotic inducible cAMP early repressor, whereas GHRH completely blocked this effect. Similar to ARVMs, in H9c2 cardiac cells, GHRH inhibited serum starvation- and isoproterenol-induced cell death and apoptosis through the same signalling pathways. Finally, GHRH improved left ventricular recovery during reperfusion and reduced infarct size in Langendorff-perfused rat hearts, subjected to ischaemia–reperfusion (I/R) injury. These effects involved PI3K/Akt signalling and were inhibited by JV-1-36. Conclusion Our findings suggest that GHRH promotes cardiac myocyte survival through multiple signalling mechanisms and protects against I/R injury in isolated rat heart, indicating a novel cardioprotective role of this hormone.
Databáze: OpenAIRE
Externí odkaz: