Dexamethasone upregulates the expression of the nuclear cofactor p300 and its interaction with C/EBPbeta in cultured myotubes.
Muscle wasting during sepsis and other catabolic conditions is, at least in part, mediated by glucocorticoids and is associated with upregulated transcription of multiple genes in the ubiquitin-proteasome proteolytic pathway. In addition to transcription factors, nuclear cofactors, including p300, regulate gene transcription. We tested the hypothesis that glucocorticoids upregulate the expression of p300 in muscle cells. Treatment of cultured L6 myotubes, a rat skeletal muscle cell line, with dexamethasone resulted in a dose- and time-dependent increase in p300 protein and mRNA levels. Surprisingly, the effect of dexamethasone on p300 levels was not inhibited by the glucocorticoid receptor (GR) antagonist RU38486 and RU38486 exerted an agonist effect on p300, increasing its expression. Co-immunoprecipitation showed that treatment of the myotubes with dexamethasone resulted in protein-protein interaction between p300 and C/EBPbeta, but not C/EBPdelta. The present results suggest that glucocorticoids upregulate the expression of p300 and its interaction with C/EBPbeta in skeletal muscle. Increased expression and activity of p300 may be involved in the regulation of gene transcription in glucocorticoid-dependent muscle wasting.
Yang
Hongmei
H
Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
Menconi
Michael J
MJ
Wei
Wei
W
Petkova
Victoria
V
Hasselgren
Per-Olof
PO
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D002460:Cell Line; D017931:DNA Primers; D003907:Dexamethasone / Q000494:pharmacology*; D050881:E1A-Associated p300 Protein; D047468:Immunoprecipitation; D009687:Nuclear Proteins / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D051381:Rats; D015534:Trans-Activators / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects*
D022782:CCAAT-Enhancer-Binding Protein-beta; D017931:DNA Primers; D009687:Nuclear Proteins; D015534:Trans-Activators; D003907:Dexamethasone; D050881:E1A-Associated p300 Protein; C494362:Ep300 protein, rat