Glucocorticoid-induced leucine zipper (GILZ) and long GILZ inhibit myogenic differentiation and mediate anti-myogenic effects of glucocorticoids.
Myogenesis is a process whereby myoblasts differentiate and fuse into multinucleated myotubes, the precursors of myofibers. Various signals and factors modulate this process, and glucocorticoids (GCs) are important regulators of skeletal muscle metabolism. We show that glucocorticoid-induced leucine zipper (GILZ), a GC-induced gene, and the newly identified isoform long GILZ ... (L-GILZ) are expressed in skeletal muscle tissue and in C2C12 myoblasts where GILZ/L-GILZ maximum expression occurs during the first few days in differentiation medium. Moreover, we observed that GC treatment of myoblasts, which increased GILZ/L-GILZ expression, resulted in reduced myotube formation, whereas GILZ and L-GILZ silencing dampened GC effects. Inhibition of differentiation caused by GILZ/L-GILZ overexpression correlated with inhibition of MyoD function and reduced expression of myogenin. Notably, results indicate that GILZ and L-GILZ bind and regulate MyoD/HDAC1 transcriptional activity, thus mediating the anti-myogenic effect of GCs.
Mesh Terms:
Alternative Splicing, Animals, Animals, Newborn, Blotting, Western, Cell Differentiation, Cells, Cultured, Chromatin Immunoprecipitation, Dexamethasone, Electrophoretic Mobility Shift Assay, Enzyme-Linked Immunosorbent Assay, Fluorescent Antibody Technique, Gene Expression Regulation, Developmental, Glucocorticoids, Immunoenzyme Techniques, Immunoprecipitation, Luciferases, Mice, Mice, Inbred C57BL, Muscle Development, Muscle, Skeletal, MyoD Protein, Myoblasts, Myogenin, Promoter Regions, Genetic, Protein Isoforms, RNA, Messenger, RNA, Small Interfering, Reverse Transcriptase Polymerase Chain Reaction, Transcription Factors, Transcription, Genetic, Transfection
Alternative Splicing, Animals, Animals, Newborn, Blotting, Western, Cell Differentiation, Cells, Cultured, Chromatin Immunoprecipitation, Dexamethasone, Electrophoretic Mobility Shift Assay, Enzyme-Linked Immunosorbent Assay, Fluorescent Antibody Technique, Gene Expression Regulation, Developmental, Glucocorticoids, Immunoenzyme Techniques, Immunoprecipitation, Luciferases, Mice, Mice, Inbred C57BL, Muscle Development, Muscle, Skeletal, MyoD Protein, Myoblasts, Myogenin, Promoter Regions, Genetic, Protein Isoforms, RNA, Messenger, RNA, Small Interfering, Reverse Transcriptase Polymerase Chain Reaction, Transcription Factors, Transcription, Genetic, Transfection
J. Biol. Chem.
Date: Apr. 02, 2010
PubMed ID: 20124407
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