Reduced amino acid availability inhibits muscle protein synthesis and decreases activity of initiation factor eIF2B
Reduced amino acid availability inhibits muscle protein synthesis and decreases activity of initiation factor eIF2B
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DOI：
10.1152/ajpendo.00094.2002
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发表时间：
2003-03-01
影响因子：
5.1
通讯作者：
Wolfe, RR
中科院分区：
文献类型：
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作者：
Kobayashi, H;Borsheim, E;Wolfe, RR
我们研究了血液透析引起的血浆氨基酸浓度降低 40% 对正常猪肌肉蛋白合成和分解速率的影响。使用[H-2(5)]苯丙氨酸和[1-C-13]亮氨酸通过示踪剂方法测量肌肉蛋白动力学，并分析股动脉和静脉样本以及组织活检。透析期间肌肉的净氨基酸释放加速。透析开始后 30 至 60 分钟之间，肌肉蛋白质合成的苯丙氨酸利用率从 45 +/- 8 的基础值降低至 25 +/- 6 nmol(.)min(-1).100 mlleg(-1)，并且在透析继续的同时替换氨基酸时会受到刺激。肌肉蛋白质分解没有变化。合成变化的信号似乎是血浆氨基酸浓度的变化，因为肌内浓度始终保持恒定。低氨基酸血症与氨基酸替代后，肌肉蛋白质合成的变化分别伴随着真核起始因子 (eIF)2B 鸟嘌呤核苷酸交换活性的减少或刺激。我们得出的结论是，血浆氨基酸浓度降低至正常基础值以下表明肌肉蛋白质合成受到抑制，而 eIF2B 活性的相应变化表明可能在介导该反应中发挥作用。
We have examined the effect of a hemodialysis-induced 40% reduction in plasma amino acid concentrations on rates of muscle protein synthesis and breakdown in normal swine. Muscle protein kinetics were measured by tracer methodology using [H-2(5)]phenylalanine and [1-C-13]leucine and analysis of femoral arterial and venous samples and tissue biopsies. Net amino acid release by muscle was accelerated during dialysis. Phenylalanine utilization for muscle protein synthesis was reduced from the basal value of 45 +/- 8 to 25 +/- 6 nmol(.)min(-1).100 ml leg(-1) between 30 and 60 min after start of dialysis and was stimulated when amino acids were replaced while dialysis continued. Muscle protein breakdown was unchanged. The signal for changes in synthesis appeared to be changes in plasma amino acid concentrations, as intramuscular concentrations remained constant throughout. The changes in muscle protein synthesis were accompanied by a reduction or stimulation, respectively, in the guanine nucleotide exchange activity of eukaryotic initiation factor (eIF)2B following hypoaminoacidemia vs. amino acid replacement. We conclude that a reduction in plasma amino acid concentrations below the normal basal value signals an inhibition of muscle protein synthesis and that corresponding changes in eIF2B activity suggest a possible role in mediating the response.