Hexarelin protects H9c2 cardiomyocytes from doxorubicin-induced cell death |
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Authors: | Filigheddu N Fubini A Baldanzi G Cutrupi S Ghè C Catapano F Broglio F Bosia A Papotti M Muccioli G Ghigo E Deghenghi R Graziani A |
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Institution: | (1) Department of Genetics, Biology and Biochemistry, University of Torino, Italy;(2) Department of Internal Medicine, Division of Cardiology, University of Torino, Italy;(3) Department of Internal Medicine, Division of Endocrinology, University of Torino, Italy;(4) Department of Pharmacology and Forensic Medicine, University of Torino, Italy;(5) Department of Biomedicat Science and Human Oncology, University of Torino, Italy;(6) Europeptides, Argenteuil, France;(7) Dept. of Medical Sciences, University. A Avogadro of Piemonte Orientale, Solaroli 17, 28100 Novara, Italy |
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Abstract: | Growth hormone secretagogues (GHSs) are synthetic peptidyl and nonpeptidyl molecules that possess strong growth hormone-releasing
activity acting on specific pituitary and hypothalamic receptor subtypes. Differently from nonpeptidyl GHSs, peptidyl molecules
such as hexarelin, a hexapeptide, possess specific high-affinity binding sites in animal and human heart and, after prolonged
treatment, protect rats in vivo from ischemiainduced myocardial damage. To verify the hypothesis that peptidyl GHSs protect
heart cells from cell death, we have investigated the cellular effects of hexarelin on H9c2 cardiomyocytes, a fetal car diomyocyte-derived
cell line, and on Hend, an endothelial cell line derived from transformed murine heart endothelium. We show that (i)H9c2 cardiomyocytes
show specific binding for 125I-Tyr-Ala-hexarelin, which is inhibited by peptidyl GHSs such as Tyr-Ala-hexarelin and hexarelin but not by the nonpeptidyl
GHS MK-0677, (ii) hexarelin promotes survival of H9c2 cardiomyocytes induced to die by doxorubicin, and (iii) that hexarelin
inhibits apoptosis, as measured by DNA fragmentation, induced in both H9c2 myocytes and endothelial cells. In conclusion,
our findings show that peptidyl GHSs such as hexarelin act as survival factors for cardiomyocytes and endothelium-derived
cells in culture. These findings suggest that the inhibitory activity of hexarelin on cardiomyocytes and endothelial cell
death could explain, at least partially, its cardioprotective effect against ischemia recorded in rats in vivo. |
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Keywords: | Hexarelin growth hormone-releasing peptides doxorubicin cardiomyocytes apoptosis |
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