C/EBPβ regulates dexamethasone-induced muscle cell atrophy and expression of atrogin-1 and MuRF1

• Published in: Journal of cellular biochemistry 2011-07, Vol.112 (7), p.1737-1748
• Main Authors: Gonnella, Patricia, Alamdari, Nima, Tizio, Steven, Aversa, Zaira, Petkova, Victoria, Hasselgren, Per-Olof
• Format: Article
• Language: English
• Subjects: Animals; Atrophy; CCAAT-Enhancer-Binding Protein-beta - genetics; CCAAT-Enhancer-Binding Protein-beta - metabolism; Cell Size - drug effects; Dexamethasone - pharmacology; Glucocorticoids; Glucocorticoids - pharmacology; Muscle Fibers, Skeletal - drug effects; Muscle Fibers, Skeletal - metabolism; Muscle Fibers, Skeletal - pathology; Muscle Proteins - genetics; Muscle Proteins - metabolism; Muscle wasting; Proteolysis; Rats; RNA Interference; Skeletal muscle; SKP Cullin F-Box Protein Ligases - genetics; SKP Cullin F-Box Protein Ligases - metabolism; Transcription factors; Transcription, Genetic - drug effects; Tripartite Motif Proteins; Ubiquitin ligases; Ubiquitin-Protein Ligases - genetics; Ubiquitin-Protein Ligases - metabolism
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.23093

Muscle wasting in catabolic patients is in part mediated by glucocorticoids and is associated with increased expression and activity of the transcription factor C/EBPβ. It is not known, however, if C/EBPβ is causally linked to glucocorticoid‐induced muscle atrophy. We used dexamethasone‐treated L6 myoblasts and myotubes to test the role of C/EBPβ in glucocorticoid‐induced expression of the muscle‐specific ubiquitin ligases atrogin‐1 and MuRF1, protein degradation, and muscle atrophy by transfecting cells with C/EBPβ siRNA. In myoblasts, silencing C/EBPβ expression with siRNA inhibited dexamethasone‐induced increase in protein degradation, atrogin‐1 and MuRF1 expression, and muscle cell atrophy. Similar effects of C/EBPβ siRNA were seen in myotubes except that the dexamethasone‐induced increase in MuRF1 expression was not affected by C/EBPβ siRNA in myotubes. In additional experiments, overexpressing C/EBPβ did not influence atrogin‐1 or MuRF1 expression in myoblasts or myotubes. Taken together, our observations suggest that glucocorticoid‐induced muscle wasting is at least in part regulated by C/EBPβ. Increased C/EBPβ expression alone, however, is not sufficient to upregulate atrogin‐1 and MuRF1 expression. J. Cell. Biochem. 112: 1737–1748, 2011. © 2011 Wiley‐Liss, Inc.