Journal
JOURNAL OF CELLULAR PHYSIOLOGY
Volume 204, Issue 1, Pages 219-226Publisher
WILEY
DOI: 10.1002/jcp.20278
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Funding
- NIDDK NIH HHS [R01 DK37908] Funding Source: Medline
- NINR NIH HHS [R01 NR08545] Funding Source: Medline
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The influence of glucocorticoids on the expression and activity of the transcription factors CCAAT/enhancer binding protein (C/EBP)beta and delta in skeletal muscle was examined by treating rats or cultured L6 myotubes with dexamethasone. Treatment of rats with 10 mg/kg of dexamethasone resulted in increased C/EBP beta and delta DNA binding activity in the extensor digitorum longus muscle as determined by electrophoretic mobility shift assay (EMSA) and supershift analysis. A similar response was noticed in dexamethasone-treated myotubes. in other experiments, myocytes were transfected with a plasmid containing a promoter construct consisting of multiple C/EBP binding elements upstream of a luciferase reporter gene. Treatment of these cells with dexamethasone resulted in a fourfold increase in luciferase activity, suggesting that glucocorticoids increase C/EBP-dependent gene activation in muscle cells. In addition, dexamethasone upregulated the protein and gene expression of C/EBP beta and delta in the myotubes in a time- and dose-dependent fashion as determined by Western blotting and real-time PCR, respectively. The results suggest that glucocorticoids increase C/EBP beta and 6 activity and expression through a direct effect in skeletal muscle.
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