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KMID : 0613820110210020242
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Journal of Life Science
2011 Volume.21 No. 2 p.242 ~ p.250
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Insulin-Like Growth Factor-I Induces Androgen Receptor Coactivator Expression in Skeletal Muscle Cells through the p38 MAPK and ERK1/2 Pathways
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Park Chan-Ho
Kim Hye-Jin
Kim Tae-Un
Lee Won-Jun
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Abstract
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Although insulin-like growth factor-I (IGF-I) and androgen receptor (AR) coactivators are well known effectors of skeletal muscle, the molecular mechanism by which signaling pathways integrating AR coactivators and IGF-I in skeletal muscle cells has not been previously examined. In this study, the effects of IGF-I treatment on the gene expression of AR coactivators in the absence of AR ligands and the roles of the p38 MAPK and ERK1/2 signaling pathways in IGF-I-induced AR coactivators induction were examined. C2C12 cells were treated with 250 ng/ml of IGF-I in the presence or absence of specific inhibitors p38 MAPK (SB203580) or ERK1/2 (PD98059). Treatment of C2C12 cells with IGF-I resulted in increased in GRIP-1, SRC-1, and ARA70 protein expression. The levels of GRIP-1, SRC-1, and ARA70 mRNA were also significantly increased after 5min of IGF-I treatment. IGF-I-induced AR coactivator proteins were significantly blocked by pharmacological inhibitors of p38 MAPK and ERK1/2 pathways. However, there was no significant effect of those inhibitors on IGF-I-induced mRNA level of AR coactivators, suggesting that AR coactivators are post-transcriptionally regulated by IGF-I. Furthermore, the present results suggest that IGF-I stimulates the expression of AR coactivators by cooperative activation of the p38 MAPK and ERK1/2 pathways in C2C12 mouse skeletal muscle cells.
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KEYWORD
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IGF-I, androgen receptor coactivator, p38 MAPK, ERK1/2, C2C12 skeletal muscle cell
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