An increase in essential amino acid availability upregulates amino acid transporter expression in human skeletal muscle
An increase in essential amino acid availability upregulates amino acid transporter expression in human skeletal muscle
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DOI：
10.1152/ajpendo.00690.2009
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发表时间：
2010-05-01
影响因子：
5.1
通讯作者：
Rasmussen, Blake B.
中科院分区：
文献类型：
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作者：
Drummond, Micah J.;Glynn, Erin L.;Rasmussen, Blake B.
Drummond MJ, Glynn EL, Fry CS, Timmerman KL, Volpi E, Rasmussen BB。必需氨基酸可用性的增加上调了人体骨骼肌中氨基酸转运蛋白的表达。[J] .中国生物医学工程学报，2016,31(2):444 - 444。首次发表于2010年2月9日；doi: 10.1152 / ajpendo.00690.2009。必需氨基酸（EAA）刺激骨骼肌靶雷帕霉素复合物1 （mTORC1）信号传导和蛋白质合成。最近有报道称，在合成代谢条件下，氨基酸（AA）转运蛋白表达的增加是雷帕霉素敏感的。本研究的目的是确定EAA可用性的增加是否会增加骨骼肌中AA转运蛋白的表达。7名年轻成年受试者（男3名，女4名）在摄入EAA （10 g）前和摄入后1-3小时对股外侧肌进行了肌肉活检。使用稳定同位素技术分析血液和肌肉样本的亮氨酸动力学。采用定量RT-PCR和免疫印迹法分别测定AA转运体和AA一般控制通路成员[一般控制非抑制因子（GCN2）、激活转录因子（ATF4）和真核起始因子(eIF2) α亚基（Ser(52)）]的mRNA和蛋白表达。摄取EAA增加了血液中亮氨酸浓度、亮氨酸向肌肉的传递、亮氨酸从血液转运到肌肉、细胞内肌肉亮氨酸浓度、核糖体蛋白S6 （Ser(240/244)）磷酸化和肌肉蛋白合成。l型AA转运体（LAT1）、CD98、钠偶联中性AA转运体（SNAT2）和质子偶联氨基酸转运体（PAT1） mRNA表达在1 h升高（P < 0.05）， LAT1蛋白表达（eaa后3 h）和SNAT2蛋白表达（eaa后2和3 h）适度升高（P < 0.05）。虽然GCN2表达和eIF2 α磷酸化没有变化，但在eaa后2 h ATF4蛋白表达达到显著性水平（P < 0.05）。我们得出结论，EAA可用性的增加上调了人类骨骼肌AA转运蛋白的表达，可能以mtorc1依赖的方式，这可能是改善AA细胞内递送所必需的适应性反应。
Drummond MJ, Glynn EL, Fry CS, Timmerman KL, Volpi E, Rasmussen BB. An increase in essential amino acid availability upregulates amino acid transporter expression in human skeletal muscle. Am J Physiol Endocrinol Metab 298: E1011-E1018, 2010. First published February 9, 2010; doi: 10.1152/ajpendo.00690.2009.-Essential amino acids (EAA) stimulate skeletal muscle mammalian target of rapamycin complex 1 (mTORC1) signaling and protein synthesis. It has recently been reported that an increase in amino acid (AA) transporter expression during anabolic conditions is rapamycin-sensitive. The purpose of this study was to determine whether an increase in EAA availability increases AA transporter expression in human skeletal muscle. Muscle biopsies were obtained from the vastus lateralis of seven young adult subjects (3 male, 4 female) before and 1-3 h after EAA ingestion (10 g). Blood and muscle samples were analyzed for leucine kinetics using stable isotopic techniques. Quantitative RT-PCR, and immunoblotting were used to determine the mRNA and protein expression, respectively, of AA transporters and members of the general AA control pathway [general control nonrepressed (GCN2), activating transcription factor (ATF4), and eukaryotic initiation factor (eIF2) alpha-subunit (Ser(52))]. EAA ingestion increased blood leucine concentration, delivery of leucine to muscle, transport of leucine from blood into muscle, intracellular muscle leucine concentration, ribosomal protein S6 (Ser(240/244)) phosphorylation, and muscle protein synthesis. This was followed with increased L-type AA transporter (LAT1), CD98, sodium-coupled neutral AA transporter (SNAT2), and proton-coupled amino acid transporter (PAT1) mRNA expression at 1 h (P < 0.05) and modest increases in LAT1 protein expression (3 h post-EAA) and SNAT2 protein expression (2 and 3 h post-EAA, P < 0.05). Although there were no changes in GCN2 expression and eIF2 alpha phosphorylation, ATF4 protein expression reached significance by 2 h post-EAA (P < 0.05). We conclude that an increase in EAA availability upregulates human skeletal muscle AA transporter expression, perhaps in an mTORC1-dependent manner, which may be an adaptive response necessary for improved AA intracellular delivery.