Ligand-independent activation of the androgen receptor by insulin-like growth factor-i and the role of the MAPK pathway in skeletal muscle cells |
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Authors: | Hye Jin Kim Won Jun Lee |
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Institution: | (1) Division of Endocrinology, Diabetology and Metabolism, Department of Internal Medicine, University of Turin, Corso Dogliotti 14, 10126 Turin, Italy; |
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Abstract: | In this study, the roles of the p38 MAPK, ERK1/2 and JNK signaling pathway in IGF-I-induced AR induction and activation were
examined. C2C12 cells were treated with IGF-I in the absence or presence of various inhibitors of p38 MAPK (SB203580), ERK1/2
(PD98059), and JNK (SP600125). Inhibition of the MAPK pathway with SB203580, PD98059, or SP600125 significantly decreased
IGF-I-induced AR phosphorylation and total AR protein expression. IGF-I-induced nuclear fraction of total AR and phosphorylated
AR were significantly inhibited by SB203580, PD98059, or SP600125. Furthermore, IGF-I-induced AR mRNA and skeletal α-actin
mRNA were blocked by those inhibitors in dose-dependent manner. Confocal images showed that IGF-I-induced AR nuclear translocation
from cytosol was significantly blocked by SB203580, PD98059, or SP600125, suggesting that the MAPK pathway regulates IGF-I-induced
AR nuclear localization in skeletal muscle cells. The present results suggest that the MAPK pathways are required for the
ligand-independent activation of AR by IGF-I in C2C12 skeletal muscle cells. |
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