RRC ID 12391
Author Yamamoto D, Ikeshita N, Matsubara T, Tasaki H, Herningtyas EH, Toda K, Iida K, Takahashi Y, Kaji H, Chihara K, Okimura Y.
Title 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.
Journal Life Sci.
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 MuRF1 mRNA levels through ghrelin receptors in myocytes.
Volume 82(9-10)
Pages 460-6
Published 2008-2-27
DOI 10.1016/j.lfs.2007.11.019
PII S0024-3205(07)00851-X
PMID 18191156
MeSH Animals Cell Line Dexamethasone / pharmacology* Dose-Response Relationship, Drug Gene Expression / drug effects Glucocorticoids / pharmacology Male Mice Muscle Cells / cytology Muscle Cells / drug effects* Muscle Cells / metabolism Muscle Proteins / genetics* Oligopeptides / pharmacology* RNA, Messenger / genetics RNA, Messenger / metabolism Rats Rats, Sprague-Dawley Receptors, Ghrelin / agonists Receptors, Ghrelin / genetics Reverse Transcriptase Polymerase Chain Reaction SKP Cullin F-Box Protein Ligases / genetics Tripartite Motif Proteins Ubiquitin-Protein Ligases / genetics*
IF 3.234
Times Cited 16
Human and Animal Cells