Protection of neonatal rat cardiac myocytes against radiation-induced damage with agonists of growth hormone-releasing hormone

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• 作者：Laura Kiscsatá ; ri^a ; Zoltá ; n Varga^a ; Andrew V. Schally^b ; Rená ; ta Gá ; spá ; r^c ; ^d ; Csilla Teré ; zia Nagy^e ; Zoltá ; n Giricz^e ; Pé ; ter Ferdinandy^d ; ^e ; Gabriella Fá ; biá ; n^a ; Zsuzsanna Kahá ; n^a ; ¹ ; Anikó ; Gö ; rbe ; MD PhD^c ; ^d ; ^e ; ¹ ; ^{aniko.gorbe@pharmahungary.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Cardiac myocytes ; Cardioprotection ; GHRH agonists ; GHRH/SV1 receptors ; Radiation damage
• 刊名：Pharmacological Research
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：111
• 期：Complete
• 页码：859-866
• 全文大小：2244 K

文摘

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 10 Gy. 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 100 nM, and MR-356 at 500 nM; 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 52 kDa 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.