Glucocorticoid-mediated regulation of utrophin levels in human muscle fibers.
Neuromuscul Disord
; 12 Suppl 1: S95-104, 2002 Oct.
Article
em En
| MEDLINE
| ID: mdl-12206803
ABSTRACT
Previous studies on transgenic mice indicate that upregulation of utrophin protein may offer a potential treatment strategy for Duchenne muscular dystrophy. We have analyzed the effect of the glucocorticoid 6alpha-methylprednisolone-21 sodium succinate on utrophin protein levels, using a cell-based assay with differentiated human myotubes, derived from biopsies of healthy individuals or Duchenne muscular dystrophy patients. We found that within 5-7 days 6alpha-methylprednisolone-21 sodium succinate increases utrophin protein up to approximately 40% in both normal and dystrophin-deficient myotubes compared to untreated control cultures. When analyzed in promoter-reporter assays 6alpha-methylprednisolone-21 sodium succinate activated a utrophin promoter A-fragment but did not activate a utrophin promoter B-fragment. Surprisingly, endogenous levels of utrophin mRNA in 6alpha-methylprednisolone-21 sodium succinate-treated muscle cells were unaltered indicating that the utrophin-inducing effect of glucocorticoids may be a result of post-transcriptional mechanisms. We have also analyzed 66 glucocorticoids for their effect on utrophin protein levels and found that glucocorticoids in general are able to induce utrophin protein in human myotubes.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Metilprednisolona
/
Fibras Musculares Esqueléticas
/
Distrofia Muscular de Duchenne
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Proteínas do Citoesqueleto
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Glucocorticoides
/
Proteínas de Membrana
Limite:
Humans
Idioma:
En
Revista:
Neuromuscul Disord
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
Suíça