Amino acid availability and age affect the leucine stimulation of protein synthesis and eIF4F formation in muscle

Amino acid availability and age affect the leucine stimulation of protein synthesis and eIF4F formation in muscle
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DOI:
10.1152/ajpendo.00302.2007
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发表时间:
2007-12-01
影响因子:
5.1
通讯作者:
Davis, Teresa A.
Davis, Teresa A.
中科院分区:
医学2区
文献类型:
--
作者:
Escobar, Jeffery;Frank, Jason W.;Davis, Teresa A.

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Escobar J,Frank JW,Suryawan A,Nguyen HV,Davis TA.氨基酸利用率和年龄影响肌肉中亮氨酸对蛋白质合成和eIF 4F形成的刺激。Am J Physiol Endocrinol Metab 293:E1615-E1621,2007。首次发表于2007年9月18日; doi:10.1152/ajpendo.00302.2007。- 我们以前已经表明,生理增加血浆亮氨酸60和120分钟增加翻译起始因子激活新生猪肌肉。虽然肌肉蛋白质合成增加亮氨酸在60分钟,它不能维持在120分钟,也许是因为血浆氨基酸(AA)的减少。在本研究中,7日龄和26日龄的猪禁食过夜,并输注亮氨酸(0或400 μ mol.kg(-1).h(-1))120分钟,以在餐后范围内提高亮氨酸。在存在或不存在替代AA混合物(不含亮氨酸)的情况下输注亮氨酸,以维持基线血浆AA水平。在两个年龄组中,AA给药可防止亮氨酸诱导的血浆AA减少。在第7天,单独的亮氨酸输注增加真核起始因子(eIF)4 E结合蛋白-1(4 E-BP 1)磷酸化,减少非活性4 E-BP 1. eIF 4 E复合物的丰度,并增加骨骼肌中活性eIF4G.eIF4E复合物的形成;亮氨酸输注与替代AA也刺激这些,以及70 kDa核糖体蛋白S6激酶,核糖体蛋白S6和eIF 4G磷酸化。在第26天,单独的亮氨酸输注增加了4 E-BP 1磷酸化,并仅减少了无活性的4 E-BP 1. eIF 4 E复合物;亮氨酸与AA也刺激了这些,以及70-kDa核糖体蛋白S6激酶和核糖体蛋白S6磷酸化。肌肉蛋白质合成增加7日龄(+60%)和26日龄(+40%)的猪注入亮氨酸和替代AA,但没有单独的亮氨酸。因此,亮氨酸刺激骨骼肌中eIF 4F形成和蛋白质合成的能力取决于AA的可用性和年龄。
Escobar J, Frank JW, Suryawan A, Nguyen HV, Davis TA. Amino acid availability and age affect the leucine stimulation of protein synthesis and eIF4F formation in muscle. Am J Physiol Endocrinol Metab 293: E1615-E1621, 2007. First published September 18, 2007; doi: 10.1152/ajpendo.00302.2007. - We have previously shown that a physiological increase in plasma leucine for 60 and 120 min increases translation initiation factor activation in muscle of neonatal pigs. Although muscle protein synthesis is increased by leucine at 60 min, it is not maintained at 120 min, perhaps because of the decrease in plasma amino acids ( AA). In the present study, 7- and 26-day-old pigs were fasted overnight and infused with leucine ( 0 or 400 mu mol.kg(-1).h(-1)) for 120 min to raise leucine within the postprandial range. The leucine was infused in the presence or absence of a replacement AA mixture ( without leucine) to maintain baseline plasma AA levels. AA administration prevented the leucine-induced reduction in plasma AA in both age groups. At 7 days, leucine infusion alone increased eukaryotic initiation factor (eIF) 4E binding protein-1 (4E-BP1) phosphorylation, decreased inactive 4E-BP1.eIF4E complex abundance, and increased active eIF4G.eIF4E complex formation in skeletal muscle; leucine infusion with replacement AA also stimulated these, as well as 70-kDa ribosomal protein S6 kinase, ribosomal protein S6, and eIF4G phosphorylation. At 26 days, leucine infusion alone increased 4E-BP1 phosphorylation and decreased the inactive 4E-BP1.eIF4E complex only; leucine with AA also stimulated these, as well as 70-kDa ribosomal protein S6 kinase and ribosomal protein S6 phosphorylation. Muscle protein synthesis was increased in 7-day-old (+60%) and 26-day-old (+40%) pigs infused with leucine and replacement AA but not with leucine alone. Thus the ability of leucine to stimulate eIF4F formation and protein synthesis in skeletal muscle is dependent on AA availability and age.