Gene interactions and pathways from curated databases and text-mining
Int J Biochem Cell Biol 2005, PMID: 15927518

Insulin-like growth factor-I inhibits dexamethasone-induced proteolysis in cultured L6 myotubes through PI3K/Akt/GSK-3beta and PI3K/Akt/mTOR-dependent mechanisms.

Li, Bing-Guo; Hasselgren, Per-Olof; Fang, Cheng-Hui

We and others reported previously that IGF-I inhibits dexamethasone-induced proteolysis in cultured L6 myotubes. Recent evidence suggests that this effect of IGF-I at least in part reflects PI3K/Akt-mediated inhibition of Foxo transcription factors. The potential role of other mechanisms, downstream of PI3K/Akt, is not well understood. Here we tested the hypothesis that PI3K/Akt-mediated inactivation of GSK-3beta and activation of mTOR contribute to the anabolic effects of IGF-I in dexamethasone-treated myotubes. Cultured L6 myotubes were treated with 1 microM dexamethasone in the absence or presence of 0.1 microg/ml of IGF-I and inhibitors of GSK-3beta and mTOR. Protein degradation was measured by determining the release of trichloroacetic acid soluble radioactivity from myotubes that had been prelabeled with (3)H-tyrosine for 48 h. IGF-I reduced basal protein breakdown rates and completely abolished the dexamethasone-induced increase in myotube proteolysis. These effects of IGF-I were associated with increased phosphorylation of Akt, GSK-3beta, and the mTOR downstream targets p70(S6K) and 4E-BP1. The PI3K inhibitor LY294002 and the mTOR inhibitor rapamycin reversed the anabolic effect of IGF-I in dexamethasone-treated myotubes. In addition, the GSK-3beta inhibitors LiCl and TDZD-8 reduced protein degradation in a similar fashion as IGF-I. Our results suggest that PI3K/Akt-mediated inactivation of GSK-3beta and activation of mTOR contribute to the anabolic effects of IGF-I in dexamethasone-treated myotubes.

Diseases/Pathways annotated by Medline MESH: MAP Kinase Signaling System
Document information provided by NCBI PubMed

Text Mining Data

mTOR → PI3K/Akt: " Here we tested the hypothesis that PI3K/Akt mediated inactivation of GSK-3beta and activation of mTOR contribute to the anabolic effects of IGF-I in dexamethasone treated myotubes "

mTOR → GSK-3beta: " Here we tested the hypothesis that PI3K/Akt mediated inactivation of GSK-3beta and activation of mTOR contribute to the anabolic effects of IGF-I in dexamethasone treated myotubes "

mTOR → PI3K/Akt: " Here we tested the hypothesis that PI3K/Akt mediated inactivation of GSK-3beta and activation of mTOR contribute to the anabolic effects of IGF-I in dexamethasone treated myotubes "

mTOR → PI3K/Akt: " Our results suggest that PI3K/Akt mediated inactivation of GSK-3beta and activation of mTOR contribute to the anabolic effects of IGF-I in dexamethasone treated myotubes "

mTOR → GSK-3beta: " Our results suggest that PI3K/Akt mediated inactivation of GSK-3beta and activation of mTOR contribute to the anabolic effects of IGF-I in dexamethasone treated myotubes "

mTOR → PI3K/Akt: " Our results suggest that PI3K/Akt mediated inactivation of GSK-3beta and activation of mTOR contribute to the anabolic effects of IGF-I in dexamethasone treated myotubes "

Manually curated Databases

No curated data.