Stimulation of myofibrillar protein degradation and expression of mRNA encoding the ubiquitin-proteasome system in C2C12 myotubes by dexamethasone

M G Thompson, A Thom, K Partridge, Karen Elise Garden, Gillian Patricia Campbell, Alexander Graham Calder, R M Palmer

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31 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)455-461
Number of pages7
JournalJournal of Cellular Physiology
Volume181
Issue number3
Publication statusPublished - Dec 1999

Keywords

  • N-TAU-methylhistidine
  • rat skeletal-muscle
  • glucocorticoid receptor
  • conjugating enzyme
  • urinary-excretion
  • messenger-RNA
  • septic rats
  • breakdown
  • proteolysis
  • turnover

Cite this

Thompson, M. G., Thom, A., Partridge, K., Garden, K. E., Campbell, G. P., Calder, A. G., & Palmer, R. M. (1999). Stimulation of myofibrillar protein degradation and expression of mRNA encoding the ubiquitin-proteasome system in C2C12 myotubes by dexamethasone. Journal of Cellular Physiology, 181(3), 455-461.