title: Protection of neonatal rat cardiac myocytes against radiation-induced damage with agonists of growth hormone-releasing hormone.
abstract: Despite the great clinical significance of radiation-induced cardiac damage, experimental investigation of its mechanisms is an unmet need in medicine. Beneficial effects of growth hormone-releasing hormone (GHRH) agonists in regeneration of the heart have been demonstrated. The aim of this study was the evaluation of the potential of modern GHRH agonistic analogs in prevention of radiation damage in an in vitro cardiac myocyte-based model. Cultures of cardiac myocytes isolated from newborn rats (NRVM) were exposed to a radiation dose of 10Gy. The effects of the agonistic analogs, JI-34 and MR-356, of human GHRH on cell viability, proliferation, their mechanism of action and the protein expression of the GHRH/SV1 receptors were studied. JI-34 and MR-356, had no effect on cell viability or proliferation in unirradiated cultures. However, in irradiated cells JI-34 showed protective effects on cell viability at concentrations of 10 and 100nM, and MR-356 at 500nM; but no such protective effect was detected on cell proliferation. Both agonistic analogs decreased radiation-induced ROS level and JI-34 interfered with the activation of SAFE/RISK pathways. Using Western blot analysis, a 52kDa protein isoform of GHRHR was detected in the samples in both irradiated and unirradiated cells. Since GHRH agonistic analogs, JI-34 and MR-356 alleviated radiation-induced damage of cardiac myocytes, they should be tested in vivo as potential protective agents against radiogenic heart damage.
authors.affiliation: Department of Oncotherapy, University of Szeged, Szeged, Hungary.
authors.forename: Laura
authors.initials: L
authors.lastname: Kiscsatári
authors.affiliation: Department of Oncotherapy, University of Szeged, Szeged, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Varga
authors.affiliation: Veterans Affairs Medical Center, Miami FL, USA and Departments of Pathology and Medicine, Divisions of Hematology/Oncology, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Schally
authors.affiliation: Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Szeged, Hungary; Pharmahungary Group, Szeged, Hungary.
authors.forename: Renáta
authors.initials: R
authors.lastname: Gáspár
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary.
authors.forename: Csilla Terézia
authors.initials: CT
authors.lastname: Nagy
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Giricz
authors.affiliation: Pharmahungary Group, Szeged, Hungary; Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Ferdinandy
authors.affiliation: Department of Oncotherapy, University of Szeged, Szeged, Hungary.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Fábián
authors.affiliation: Department of Oncotherapy, University of Szeged, Szeged, Hungary.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Kahán
authors.affiliation: Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Szeged, Hungary; Pharmahungary Group, Szeged, Hungary; Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary. Electronic address: aniko.gorbe@pharmahungary.com.
authors.forename: Anikó
authors.initials: A
authors.lastname: Görbe
mesh_terms: D000527:Alprostadil / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D066126:Cardiotoxicity; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D013007:Growth Hormone-Releasing Hormone / Q000819:agonists* / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D018013:Receptors, Neuropeptide / Q000819:agonists / Q000378:metabolism; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000819:agonists / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects
chemical_list: C587256:GH-RH(1-29), desaminotyrosyl(1)-ornithyl(12,21)-alpha-aminobutryic acid(15)-norleucyl(27)-aspartyl(28)-agmatine(29)-; D010446:Peptide Fragments; D011837:Radiation-Protective Agents; D017382:Reactive Oxygen Species; D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; C039542:somatocrinin receptor; C060276:MR 356; D013007:Growth Hormone-Releasing Hormone; D000527:Alprostadil; C048250:somatotropin releasing hormone receptor
keywords: Cardiac myocytes; Cardioprotection; GHRH agonists; GHRH/SV1 receptors; Radiation damage