The transcription factors NF-kappab and AP-1 are differentially regulated in skeletal muscle during sepsis.
Sepsis is associated with increased muscle proteolysis and upregulated transcription of several genes in the ubiquitin-proteasome proteolytic pathway. Glucocorticoids are the most important mediator of sepsis-induced muscle cachexia. Here, we examined the influence of sepsis in rats on the transcription factors NF-kappaB and AP-1 in skeletal muscle and the potential role of glucocorticoids in the regulation of these transcription factors. Sepsis was induced by cecal ligation and puncture (CLP). Control rats were sham-operated. NF-kappaB and AP-1 DNA binding activity was determined by electrophoretic mobility shift assay (EMSA) in extensor digitorum longus muscles at different time points up to 16 h after sham-operation or CLP. Sepsis resulted in an early (4 h) upregulation of NF-kappaB activity followed by inhibited NF-kappaB activity at 16 h. AP-1 binding activity was increased at all time points studied during the septic course. When rats were treated with the glucocorticoid receptor antagonist RU38486, NF-kappaB activity increased, whereas AP-1 activity was not influenced by RU38486. The results suggest that NF-kappaB and AP-1 are differentially regulated in skeletal muscle during sepsis and that glucocorticoids may regulate some but not all transcription factors in septic muscle.
Department of Surgery, University of Cincinnati, Cincinnati, Ohio, 45267-0558, USA.
C G
CG
Penner
G
G
Gang
C
C
Wray
J E
JE
Fischer
P O
PO
Hasselgren
D000818:Animals; D004247:DNA / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006727:Hormone Antagonists / Q000494:pharmacology; D020672:I-kappa B Proteins / Q000378:metabolism; D007700:Kinetics; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors; D018805:Sepsis / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D006727:Hormone Antagonists; D020672:I-kappa B Proteins; D016328:NF-kappa B; D011965:Receptors, Glucocorticoid; D018808:Transcription Factor AP-1; D015735:Mifepristone; D004247:DNA