GHRP-2, a GHS-R agonist, directly acts on myocytes to attenuate the dexamethasone-induced expressions of muscle-specific ubiquitin ligases, Atrogin-1 and MuRF1

Life Sciences
Daisuke YamamotoYasuhiko Okimura

Abstract

Recent reports suggest that Atrogin-1 and MuRF1, E3 ubiquitin ligases, play a pivotal role in muscle atrophy. In the present study, effect of Growth Hormone Releasing Peptide-2 (GHRP-2), a GH secretagogue receptor (GHS-R) agonist, on the expressions of Atrogin-1 and MuRF1 in vivo rat muscles was examined. Dexamethasone administration increased Atrogin-1 mRNA level in rat soleus muscle. The increased mRNA level of Atrogin-1 was significantly attenuated by GHRP-2. In addition, GHRP-2 decreased MuRF1 mRNA level irrespective of the presence of dexamethasone. Although IGF-I is a well-known protective factor for muscle atrophy, GHRP-2 did not influence plasma IGF-I levels and IGF-I mRNA levels in muscles. To clarify a direct effect of GHRP-2, differentiated C2C12 myocytes were used. Ten micrometer dexamethasone increased both Atrogin-1 and MuRF1 mRNA levels in C2C12 cells. GHRP-2 attenuated dexamethasone-induced expression of them dose-dependently and decreased the basal level of MuRF1 mRNA. The suppressive effect on the expressions of Atrogin-1 and MuRF1 by GHRP-2 was blocked by [D-Lys(3)]-GHRP-6, a GHS-R1a blocker, suggesting the effect of GHRP-2 was mediated through GHS-R1a. Taken together, GHRP-2 directly attenuates Atrogin-1 and...Continue Reading

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Citations

May 18, 2010·Current Opinion in Clinical Nutrition and Metabolic Care·Per-Olof HasselgrenSteven Tizio
Jun 17, 2011·Journal of Endocrinological Investigation·M A MinettoG D'Antona
Mar 21, 2013·Journal of Gastroenterology·Hajime SuzukiAkio Inui
Mar 6, 2012·European Journal of Internal Medicine·Takashi Akamizu, Kenji Kangawa
Apr 9, 2011·Journal of Cachexia, Sarcopenia and Muscle·Takashi Akamizu, Kenji Kangawa
Jul 26, 2015·Journal of Translational Medicine·Annamaria De LucaDiana Conte Camerino
Sep 27, 2014·European Journal of Pharmacology·Hironobu TsubouchiMasamitsu Nakazato
May 5, 2017·Clinical Medicine Insights. Cardiology·Jorge Berlanga-AcostaGerardo Guillén-Nieto
Jun 15, 2021·Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society·Ran SawaYasuhiko Okimura

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