RRC ID |
12391
|
著者 |
Yamamoto D, Ikeshita N, Matsubara T, Tasaki H, Herningtyas EH, Toda K, Iida K, Takahashi Y, Kaji H, Chihara K, Okimura Y.
|
タイトル |
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.
|
ジャーナル |
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.
|
巻・号 |
82(9-10)
|
ページ |
460-6
|
公開日 |
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 |
3.647
|
引用数 |
22
|
WOS 分野
|
MEDICINE, RESEARCH & EXPERIMENTAL
PHARMACOLOGY & PHARMACY
|
リソース情報 |
ヒト・動物細胞 |
C2C12(RCB0987) |