Addition of the synthetic glucocorticoid, dexamethasone (Dex) to serum-deprived C2C12 myotubes elicited time- and concentration-dependent changes in N-tau-methylhistidine (3-MH), a marker of myofibrillar protein degradation. Within 24 h, 100 nM Dex significantly decreased the cell content of 3-MH and increased release into the medium. Both of these responses had increased in magnitude by 48 h and then declined toward basal values by 72 h. The increase in the release of 3-MH closely paralleled its loss from the cell protein. Furthermore, Dex also decreased the 3-MH:total cell protein ratio, suggesting that myofibrillar proteins were being preferentially degraded. Incubation of myotubes with the peptide aldehyde, MC-132, an inhibitor of proteolysis by the (ATP)-ubiquitin (Ub)-dependent proteasome, prevented both the basal release of 3-MH (> 95%) and the increased release of 3-MH into the medium in response to Dex (> 95%). Northern hybridization studies demonstrated that Dex also elicited similar time- and concentration-dependent increases in the expression of mRNA encoding two components (14 kDa E-2 Ub-conjugating enzyme and Ub) of the ATP-Ub-dependent pathway. The data demonstrate that Dex stimulates preferential hydrolysis of myofibrillar proteins in C2C12 myotubes and suggests that the ATP-Ub-dependent pathway is involved in this response. (C) 1999 Wiley-Liss, Inc.
|Number of pages||7|
|Journal||Journal of Cellular Physiology|
|Publication status||Published - Dec 1999|
- rat skeletal-muscle
- glucocorticoid receptor
- conjugating enzyme
- septic rats