TNF-binding protein ameliorates inhibition of skeletal muscle protein synthesis during sepsis.
TNF-binding protein ameliorates inhibition of skeletal muscle protein synthesis during sepsis.
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TNF 结合蛋白可改善脓毒症期间骨骼肌蛋白合成的抑制。
DOI：
10.1152/ajpendo.1999.276.4.e611
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Vary,TC
中科院分区：
文献类型：
--
作者：
Cooney,R;Kimball,SR;Eckman,R;Maish3rd,G;Shumate,M;Vary,TC
我们研究了四组大鼠在脓毒症过程中肿瘤坏死因子结合蛋白(TNFBP)对肌肉蛋白质合成调节机制的影响：对照组；对照组+TNFBP；脓毒症；脓毒症+TNFBP。脓毒症诱导前4h开始每日注射生理盐水(1.0ml)或TNFBP(1 mg/kg，1.0ml)。5d后观察TNFBP对腓肠肌重量、蛋白质含量及蛋白质合成率的影响。与对照组相比，脓毒症通过抑制翻译效率，使蛋白质合成速度降低了35%。蛋白质合成的减少伴随着蛋白质含量和肌肉重量的类似减少。用TNFBP治疗脓毒症动物5天可阻止脓毒症引起的蛋白质合成抑制，并将翻译效率恢复到对照水平。对照组大鼠经TNFBP处理5d后，肌肉蛋白质含量和蛋白质合成均无明显变化。我们还评估了调节翻译效率的潜在机制。脓毒症不改变p70S6蛋白的磷酸化状态。脓毒症使腓肠肌真核细胞起始因子2Bε(eIF2Bε)含量降低，但不影响eIF2α的表达。应用肿瘤坏死因子结合蛋白治疗脓毒症大鼠可阻止eIF2Bε含量下降。TNFBP可改善脓毒症引起的腓肠肌蛋白质代谢变化，提示肿瘤坏死因子在脓毒症过程中的作用。这些数据表明，在脓毒症过程中，肿瘤坏死因子可能通过减少特定起始因子的表达而损害肌肉蛋白质的合成。
We examined the effects of TNF-binding protein (TNFBP) on regulatory mechanisms of muscle protein synthesis during sepsis in four groups of rats: Control; Control+TNFBP; Septic; and Septic+TNFBP. Saline (1.0 ml) or TNFBP (1 mg/kg, 1.0 ml) was injected daily starting 4 h before the induction of sepsis. The effect of TNFBP on gastrocnemius weight, protein content, and the rate of protein synthesis was examined 5 days later. Sepsis reduced the rate of protein synthesis by 35% relative to controls by depressing translational efficiency. Decreases in protein synthesis were accompanied by similar reductions in protein content and muscle weight. Treatment of septic animals with TNFBP for 5 days prevented the sepsis-induced inhibition of protein synthesis and restored translational efficiency to control values. TNFBP treatment of Control rats for 5 days was without effect on muscle protein content or protein synthesis. We also assessed potential mechanisms regulating translational efficiency. The phosphorylation state of p70S6kinase was not altered by sepsis. Sepsis reduced the gastrocnemius content of eukaryotic initiation factor 2Bε (eIF2Bε), but not eIF2α. The decrease in eIF2Bε content was prevented by treatment of septic rats with TNFBP. TNFBP ameliorates the sepsis-induced changes in protein metabolism in gastrocnemius, indicating a role for TNF in the septic process. The data suggest that TNF may impair muscle protein synthesis by reducing expression of specific initiation factors during sepsis.