The effect of glucocorticoids on the accumulation of utrophin by cultured normal and dystrophic human skeletal muscle satellite cells.
Human muscle cultures undergo a long-term loss of myotubes and a decline in dystrophin content, which can be prevented by glucocorticoid treatment of the cultures. We confirmed these findings and extended them to show that the utrophin content of control and dexamethasone-treated normal myotube cultures is not significantly different. In contrast to normal cultures, the utrophin content of long-term dexamethasone-treated DMD myotube cultures was significantly greater than that of the corresponding untreated cultures. Utrophin mRNA transcript levels normalized to total poly (A) were unaffected by dexamethasone treatment of either normal or DMD myotube cultures, suggesting the effect of dexamethasone on utrophin accumulation by DMD cultures is mediated post-transcriptionally. A combination of an increase in myotube numbers and lack of competition with dystrophin for membrane-binding sites in DMD myotubes may explain the distinct effects of dexamethasone on utrophin levels in normal and DMD cultures.
Pasquini
F
F
Neuromuscular Research Group, Montreal Neurological Institute, QC, Canada.
Guerin
C
C
Blake
D
D
Davies
K
K
Karpati
G
G
Holland
P
P
D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000187:drug effects* / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016189:Dystrophin / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D008565:Membrane Proteins; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology*; D009136:Muscular Dystrophies / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D049411:Utrophin
D003598:Cytoskeletal Proteins; D016189:Dystrophin; D005938:Glucocorticoids; D008565:Membrane Proteins; D012333:RNA, Messenger; D049411:Utrophin; D003907:Dexamethasone