Amino acids stimulate translation initiation and protein synthesis through an Akt-independent pathway in human skeletal muscle
Amino acids stimulate translation initiation and protein synthesis through an Akt-independent pathway in human skeletal muscle
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DOI：
10.1210/jc.2002-020424
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发表时间：
2002-12-01
影响因子：
5.8
通讯作者：
Barrett, EJ
中科院分区：
文献类型：
--
作者：
Liu, ZQ;Jahn, LA;Barrett, EJ
啮齿类动物体内和体外研究表明，氨基酸（AA）不仅是蛋白质合成的底物，而且还作为营养信号促进骨骼肌mRNA翻译和蛋白质合成。然而，这些发现与正常人的生理相关性尚不确定。为探讨AA对人骨骼肌蛋白质合成的调节作用，我们将AA混合液（10%Travesol）全身注入10名健康男性志愿者体内，持续6小时。分别测定注射AA前后前臂肌蛋白质合成和降解（苯丙氨酸示踪法）以及股外侧肌蛋白激酶B（或Akt）、真核起始因子4 E结合蛋白1（4 E-binding protein 1）和核糖体蛋白S6激酶（P70（S6 K））的磷酸化水平。我们还研究了AA是否影响尿氮排泄和全身蛋白质周转。AA输注后3 h（P < 0.002）和6 h（P < 0.02）的苯丙氨酸净平衡均明显改善。苯丙氨酸平衡的这种改善仅来自蛋白质合成的增加（3小时时P = 0.02，6小时时P < 0.003），因为蛋白质降解没有改变。AA还显著降低了全身苯丙氨酸通量（P < 0.004）。AA不能激活Akt的Ser（473）磷酸化，但显著增加真核起始因子4 E结合蛋白1（P < 0.04）和p70（S6 K）的磷酸化（P < 0.001）。我们的结论是，AA直接作为营养信号，刺激蛋白质合成，通过Akt非依赖性激活蛋白质合成装置在人骨骼肌。
Studies in vitro as well as in vivo in rodents have suggested that amino acids (AA) not only serve as substrates for protein synthesis, but also as nutrient signals to enhance mRNA translation and protein synthesis in skeletal muscle. However, the physiological relevance of these findings to normal humans is uncertain. To examine whether AA regulate the protein synthetic apparatus in human skeletal muscle, we infused an AA mixture (10% Travesol) systemically into 10 young healthy male volunteers for 6 h. Forearm muscle protein synthesis and degradation (phenylalanine tracer method) and the phosphorylation of protein kinase B (or Akt), eukaryotic initiation factor 4E-binding protein 1, and ribosomal protein S6 kinase (P70(S6K)) in vastus lateralis muscle were measured before and after AA infusion. We also examined whether AA affect urinary nitrogen excretion and whole body protein turnover.Postabsorptively all subjects had negative forearm phenylalanine balances. AA infusion significantly improved the net phenylalanine balance at both 3 h (P < 0.002) and 6 h (P < 0.02). This improvement in phenylalanine balance was solely from increased protein synthesis (P = 0.02 at 3 h and P < 0.003 at 6 h), as protein degradation was not changed. AA also significantly decreased whole body phenylalanine flux (P < 0.004). AA did not activate Akt phosphorylation at Ser(473), but significantly increased the phosphorylation of both eukaryotic initiation factor 4E-binding protein 1 (P < 0.04) and p70(S6K) (p < 0.001). We conclude that AA act directly as nutrient signals to stimulate protein synthesis through Akt-independent activation of the protein synthetic apparatus in human skeletal muscle.