sirolimus and 4-benzyl-2-methyl-1-2-4-thiadiazolidine-3-5-dione

sirolimus has been researched along with 4-benzyl-2-methyl-1-2-4-thiadiazolidine-3-5-dione* in 1 studies

Other Studies

1 other study(ies) available for sirolimus and 4-benzyl-2-methyl-1-2-4-thiadiazolidine-3-5-dione

ArticleYear
Insulin-like growth factor-I inhibits dexamethasone-induced proteolysis in cultured L6 myotubes through PI3K/Akt/GSK-3beta and PI3K/Akt/mTOR-dependent mechanisms.
    The international journal of biochemistry & cell biology, 2005, Volume: 37, Issue:10

    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.

    Topics: Animals; Cells, Cultured; Chromones; Dexamethasone; Dose-Response Relationship, Drug; Flavonoids; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Humans; Insulin-Like Growth Factor I; Lithium Chloride; MAP Kinase Signaling System; Models, Biological; Morpholines; Muscle Fibers, Skeletal; Muscle Proteins; Phosphatidylinositol 3-Kinases; Protein Kinases; Rats; Sirolimus; Thiadiazoles; TOR Serine-Threonine Kinases

2005