DEXAMETHASONE STIMULATES PROTEASOME-DEPENDENT AND CALCIUM-DEPENDENT PROTEOLYSIS IN CULTURED L6-MYOTUBES

The effect of dexamethasone on protein degradation and the involvement of different protealylic pathways were examined in cultured L6 myotub es. Treatment of the cells with dexamethasone resulted in an approxima tely 20% increase in protein degradation at a hormone concentration of 10(-7) to 10(-6) M. By using various proteolytic blockers, evidence w as found that the dexamethasone-induced increase in protein breakdown mainly reflected energy-proteasome-dependent proteolysis and to a less er extent calcium-dependent protein breakdown. In contrast, the hormon e treatment did not increase lysosomal proteolysis, mRNA levels for ca thepsin B, ubiquitin, and the proteasome subunit C3 were increased by dexamethasone. The results suggest that glucocorticoids stimulate calc ium and energy-proteasome-dependent muscle proteolysis and that change s in mRNA levels for proteolytic enzymes do not necessarily reflect th e involvement of different proteolytic pathways.