Penner C G, Gang G, Wray C, Fischer J E, Hasselgren P O
Department of Surgery, University of Cincinnati, Cincinnati, Ohio, 45267-0558, USA.
Biochem Biophys Res Commun. 2001 Mar;281(5):1331-6. doi: 10.1006/bbrc.2001.4497.
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.
脓毒症与肌肉蛋白水解增加以及泛素 - 蛋白酶体蛋白水解途径中多个基因的转录上调有关。糖皮质激素是脓毒症诱导的肌肉恶病质的最重要介质。在此，我们研究了大鼠脓毒症对骨骼肌中转录因子NF-κB和AP-1的影响，以及糖皮质激素在这些转录因子调节中的潜在作用。通过盲肠结扎和穿刺（CLP）诱导脓毒症。对照大鼠进行假手术。在假手术或CLP后长达16小时的不同时间点，通过电泳迁移率变动分析（EMSA）测定趾长伸肌中NF-κB和AP-1的DNA结合活性。脓毒症导致NF-κB活性早期（4小时）上调，随后在16小时时NF-κB活性受到抑制。在脓毒症病程中研究的所有时间点，AP-1结合活性均增加。当用糖皮质激素受体拮抗剂RU38486治疗大鼠时，NF-κB活性增加，而AP-1活性不受RU38486影响。结果表明，脓毒症期间骨骼肌中NF-κB和AP-1受到不同调节，并且糖皮质激素可能调节脓毒症肌肉中的一些但不是全部转录因子。
