Dexamethasone stimulates proteasome- and calcium-dependent proteolysis in cultured L6 myotubes

• Published in: Shock (Augusta, Ga.) Vol. 10; no. 4; p. 298
• Main Authors: Wang, L, Luo, G J, Wang, J J, Hasselgren, P O
• Format: Journal Article
• Language: English
• Published: United States 01.10.1998
• Subjects: Adenosine Triphosphate - analysis; Adenosine Triphosphate - metabolism; Animals; Calcium - metabolism; Calpain - drug effects; Calpain - genetics; Cathepsin B - drug effects; Cathepsin B - genetics; Cathepsin D - drug effects; Cathepsin D - genetics; Cells, Cultured; Chloroquine - pharmacology; Cysteine Endopeptidases - drug effects; Cysteine Endopeptidases - metabolism; Deoxyglucose - pharmacology; Dexamethasone - pharmacology; Leucine - analogs & derivatives; Leucine - pharmacology; Leupeptins - pharmacology; Methylamines - pharmacology; Mifepristone - pharmacology; Multienzyme Complexes - drug effects; Multienzyme Complexes - metabolism; Muscle, Skeletal - cytology; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Proteasome Endopeptidase Complex; Proteins - drug effects; Proteins - metabolism; Rats; Tyrosine - metabolism; Ubiquitins - drug effects; Ubiquitins - genetics
• ISSN: 1073-2322
• DOI: 10.1097/00024382-199810000-00011

The effect of dexamethasone on protein degradation and the involvement of different proteolytic pathways were examined in cultured L6 myotubes. Treatment of the cells with dexamethasone resulted in an approximately 20% increase in protein degradation at a hormone concentration of 10(-7) to 10(-6) M. By using various proteolytic blockers, evidence was found that the dexamethasone-induced increase in protein breakdown mainly reflected energy-proteasome-dependent proteolysis and to a lesser extent calcium-dependent protein breakdown. In contrast, the hormone treatment did not increase lysosomal proteolysis. mRNA levels for cathepsin B, ubiquitin, and the proteasome subunit C3 were increased by dexamethasone. The results suggest that glucocorticoids stimulate calcium and energy-proteasome-dependent muscle proteolysis and that changes in mRNA levels for proteolytic enzymes do not necessarily reflect the involvement of different proteolytic pathways.