Dexamethasone stimulates proteasome- and calcium-dependent proteolysis in cultured L6 myotubes.
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.
Wang
L
L
Department of Surgery, University of Cincinnati and Shriners Hospital for Children, Ohio 45267, USA.
Luo
G J
GJ
Wang
J J
JJ
Hasselgren
P O
PO
D000255:Adenosine Triphosphate / Q000032:analysis / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002154:Calpain / Q000187:drug effects / Q000235:genetics; D002401:Cathepsin B / Q000187:drug effects / Q000235:genetics; D002402:Cathepsin D / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000187:drug effects / Q000378:metabolism*; D003847:Deoxyglucose / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D007976:Leupeptins / Q000494:pharmacology; D008744:Methylamines / Q000494:pharmacology; D015735:Mifepristone / Q000494:pharmacology; D009097:Multienzyme Complexes / Q000187:drug effects / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D014443:Tyrosine / Q000378:metabolism; D014452:Ubiquitins / Q000187:drug effects / Q000235:genetics
D007976:Leupeptins; D008744:Methylamines; D009097:Multienzyme Complexes; D011506:Proteins; D014452:Ubiquitins; D015735:Mifepristone; D014443:Tyrosine; D003907:Dexamethasone; D002738:Chloroquine; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; C027451:methylamine; D002154:Calpain; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; D002402:Cathepsin D; D046988:Proteasome Endopeptidase Complex; D007930:Leucine; C032854:leupeptin; C024974:E 64; D002118:Calcium