University of Texas Medical Branch, Department of Nutrition and Metabolism, Division of Rehabilitation Sciences, Sealy Center on Aging, 301 Univ. Blvd., Galveston, TX 77555-1144, USA.
J Appl Physiol (1985). 2011 Jul;111(1):135-42. doi: 10.1152/japplphysiol.01408.2010. Epub 2011 Apr 28.
Amino acid transporters and mammalian target of rapamycin complex 1 (mTORC1) signaling are important contributors to muscle protein anabolism. Aging is associated with reduced mTORC1 signaling following resistance exercise, but the role of amino acid transporters is unknown. Young (n = 13; 28 ± 2 yr) and older (n = 13; 68 ± 2 yr) subjects performed a bout of resistance exercise. Skeletal muscle biopsies (vastus lateralis) were obtained at basal and 3, 6, and 24 h postexercise and were analyzed for amino acid transporter mRNA and protein expression and regulators of amino acid transporter transcription utilizing real-time PCR and Western blotting. We found that basal amino acid transporter expression was similar in young and older adults (P > 0.05). Exercise increased L-type amino acid transporter 1/solute-linked carrier (SLC) 7A5, CD98/SLC3A2, sodium-coupled neutral amino acid transporter 2/SLC38A2, proton-assisted amino acid transporter 1/SLC36A1, and cationic amino acid transporter 1/SLC7A1 mRNA expression in both young and older adults (P < 0.05). L-type amino acid transporter 1 and CD98 protein increased only in younger adults (P < 0.05). eukaryotic initiation factor 2 α-subunit (S52) increased similarly in young and older adults postexercise (P < 0.05). Ribosomal protein S6 (S240/244) and activating transcription factor 4 nuclear protein expression tended to be higher in the young, while nuclear signal transducer and activator of transcription 3 (STAT3) (Y705) was higher in the older subjects postexercise (P < 0.05). These results suggest that the rapid upregulation of amino acid transporter expression following resistance exercise may be regulated differently between the age groups, but involves a combination of mTORC1, activating transcription factor 4, eukaryotic initiation factor 2 α-subunit, and STAT3. We propose an increase in amino acid transporter expression may contribute to enhanced amino acid sensitivity following exercise in young and older adults. In older adults, the increased nuclear STAT3 phosphorylation may be indicative of an exercise-induced stress response, perhaps to export amino acids from muscle cells.
氨基酸转运体和哺乳动物雷帕霉素靶蛋白复合物 1(mTORC1)信号是肌肉蛋白质合成的重要贡献者。衰老与抗阻运动后 mTORC1 信号降低有关,但氨基酸转运体的作用尚不清楚。本研究纳入了年轻(n = 13;28 ± 2 岁)和老年(n = 13;68 ± 2 岁)受试者,让他们进行一次抗阻运动。在运动前、运动后 3、6 和 24 小时采集股外侧肌活检标本,并利用实时 PCR 和 Western 印迹法分析氨基酸转运体 mRNA 和蛋白表达以及氨基酸转运体转录的调节因子。结果发现,年轻和老年成年人的基础氨基酸转运体表达相似(P > 0.05)。运动增加了年轻和老年成年人的 L 型氨基酸转运体 1/溶质载体(SLC)7A5、CD98/SLC3A2、钠耦合中性氨基酸转运体 2/SLC38A2、质子辅助氨基酸转运体 1/SLC36A1 和阳离子氨基酸转运体 1/SLC7A1 mRNA 表达(P < 0.05)。仅在年轻成年人中,L 型氨基酸转运体 1 和 CD98 蛋白增加(P < 0.05)。运动后,年轻和老年成年人的真核起始因子 2α 亚基(S52)增加相似(P < 0.05)。核糖体蛋白 S6(S240/244)和激活转录因子 4 核蛋白表达在年轻人中趋于更高,而运动后老年人的核信号转导和转录激活因子 3(STAT3)(Y705)更高(P < 0.05)。这些结果表明,抗阻运动后氨基酸转运体表达的快速上调可能在不同年龄组之间受到不同的调节,但涉及 mTORC1、激活转录因子 4、真核起始因子 2α 亚基和 STAT3。我们提出,氨基酸转运体表达的增加可能有助于增强年轻和老年成年人运动后的氨基酸敏感性。在老年人中,增加的核 STAT3 磷酸化可能表明运动引起的应激反应,也许是为了将氨基酸从肌肉细胞中输出。