C/EBPβ Regulates Dexamethasone-Induced Muscle Cell Atrophy and Expression of Atrogin-1 and MuRF1

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