GSK-3beta negatively regulates skeletal myotube hypertrophy |
| |
Authors: | Vyas Dharmesh R Spangenburg Espen E Abraha Tsghe W Childs Thomas E Booth Frank W |
| |
Affiliation: | Department of Veterinary Biomedical Sciences, and the Dalton Cardiovascular Institute, University of Missouri, Columbia, Missouri 65211, USA. |
| |
Abstract: | Todetermine whether changes in glycogen synthase kinase-3 (GSK-3)phosphorylation contribute to muscle hypertrophy, we delineated theeffects of GSK-3 activity on C2C12 myotubesize. We also examined possible insulin-like growth factor I (IGF-I) signaling of NFAT (nuclear factors of activated T cells)-inducible geneactivity and possible modulation of NFAT activation by GSK-3. Application of IGF-I (250 ng/ml) or LiCl (10 mM) alone (i.e., bothinhibit GSK-3 activity) increased the area ofC2C12 myotubes by 80 and 85%, respectively.The application of IGF-I (250 ng/ml) elevated GSK-3 phosphorylationand reduced GSK-3 kinase activity by ~800% and ~25%,respectively. LY-294002 (100 µM) and wortmannin (150 µM), specificinhibitors of phosphatidylinositol 3'-kinase, attenuated IGF-I-inducedGSK-3 phosphorylation by 67 and 92%, respectively. IGF-I suppressedthe kinase activity of GSK-3. IGF-I (250 ng/ml), but not LiCl (10 mM), induced an increase in NFAT-activated luciferase reporteractivity. Cotransfection of a constitutively active GSK-3(cGSK-3) inhibited the induction by IGF-I of NFAT-inducible reporteractivity. LiCl, which inhibits GSK-3, removed the block by cGSK-3on IGF-I-inducible NFAT-responsive reporter gene activity. These datasuggest that the IGF-I-induced increase in skeletal myotube size issignaled, in part, through the inhibition of GSK-3. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
| 点击此处可从《American journal of physiology. Cell physiology》浏览原始摘要信息 |
|
点击此处可从《American journal of physiology. Cell physiology》下载全文 |
|