Bed rest impairs skeletal muscle amino acid transporter expression, mTORC1 signaling, and protein synthesis in response to essential amino acids in older adults
Bed rest impairs skeletal muscle amino acid transporter expression, mTORC1 signaling, and protein synthesis in response to essential amino acids in older adults
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DOI：
10.1152/ajpendo.00603.2011
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发表时间：
2012-05-01
影响因子：
5.1
通讯作者：
Volpi, Elena
中科院分区：
文献类型：
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作者：
Drummond, Micah J.;Dickinson, Jared M.;Volpi, Elena
Drummond MJ，Dickinson JM，Fry CS，步行者DK，Gundermann DM，Reidy PT，Timmerman KL，Markofski MM，Paddon-Jones D，Rasmussen BB，Volpi E.卧床休息损害骨骼肌氨基酸转运蛋白的表达，mTORC 1信号，和蛋白质合成响应于老年人的必需氨基酸。Am J Physiol Endocrinol Metab 302：E1113-E1122，2012。首次发布于2012年2月14日; doi：10.1152/ajpendo.00603.2011。-卧床休息期间的骨骼肌萎缩至少部分归因于基础肌肉蛋白合成（MPS）较慢。必需氨基酸（EAA）刺激哺乳动物雷帕霉素靶蛋白（mTORC 1）信号传导、氨基酸转运蛋白表达和MPS，并且是维持肌肉质量所必需的，但是没有关于不活动对这种合成代谢机制的影响的数据。我们假设卧床休息通过降低mTORC 1信号传导和老年人氨基酸转运蛋白表达来减弱MPS的EAA刺激，从而降低老年人的肌肉质量。6名健康老年人（67 +/- 2岁）参加了一项为期7天的卧床休息研究。我们使用稳定同位素示踪剂，蛋白质印迹法和实时qPCR来确定卧床休息对MPS，肌肉mTORC 1信号传导和氨基酸转运蛋白表达和含量的影响，在吸收后状态和急性EAA摄入后。卧床休息使腿部瘦体重下降约4%（P < 0.05），吸收后mTOR蛋白水平升高（P < 0.05），而吸收后MPS无变化（P > 0.05）。卧床前急性EAA摄入增加MPS、mTOR（Ser（2448））、S6激酶1（Thr（389）、Thr（421）/Ser（424））和核糖体蛋白S6（Ser（240/244））磷酸化、转录激活因子4、L型氨基酸转运体1和钠偶联氨基酸转运体2蛋白含量（P < 0.05）。然而，卧床休息减弱了EAA诱导的MPS、mTORC 1信号传导和氨基酸转运蛋白含量的增加。我们的结论是，老年人卧床休息可显着减弱EAA诱导的MPS增加，其机制涉及mTORC 1信号传导和氨基酸转运蛋白含量减少。总之，我们的数据表明，钝EAA刺激MPS可能有助于肌肉损失与老年人的不活动。
Drummond MJ, Dickinson JM, Fry CS, Walker DK, Gundermann DM, Reidy PT, Timmerman KL, Markofski MM, Paddon-Jones D, Rasmussen BB, Volpi E. Bed rest impairs skeletal muscle amino acid transporter expression, mTORC1 signaling, and protein synthesis in response to essential amino acids in older adults. Am J Physiol Endocrinol Metab 302: E1113-E1122, 2012. First published February 14, 2012; doi:10.1152/ajpendo.00603.2011.-Skeletal muscle atrophy during bed rest is attributed, at least in part, to slower basal muscle protein synthesis (MPS). Essential amino acids (EAA) stimulate mammalian target of rapamycin (mTORC1) signaling, amino acid transporter expression, and MPS and are necessary for muscle mass maintenance, but there are no data on the effect of inactivity on this anabolic mechanism. We hypothesized that bed rest decreases muscle mass in older adults by blunting the EAA stimulation of MPS through reduced mTORC1 signaling and amino acid transporter expression in older adults. Six healthy older adults (67 +/- 2 yr) participated in a 7-day bed rest study. We used stable isotope tracers, Western blotting, and real-time qPCR to determine the effect of bed rest on MPS, muscle mTORC1 signaling, and amino acid transporter expression and content in the postabsorptive state and after acute EAA ingestion. Bed rest decreased leg lean mass by similar to 4% (P < 0.05) and increased postabsorptive mTOR protein (P < 0.05) levels while postabsorptive MPS was unchanged (P > 0.05). Before bed rest acute EAA ingestion increased MPS, mTOR (Ser(2448)), S6 kinase 1 (Thr(389), Thr(421)/Ser(424)), and ribosomal protein S6 (Ser(240/244)) phosphorylation, activating transcription factor 4, L-type amino acid transporter 1 and sodium-coupled amino acid transporter 2 protein content (P < 0.05). However, bed rest blunted the EAA-induced increase in MPS, mTORC1 signaling, and amino acid transporter protein content. We conclude that bed rest in older adults significantly attenuated the EAA-induced increase in MPS with a mechanism involving reduced mTORC1 signaling and amino acid transporter protein content. Together, our data suggest that a blunted EAA stimulation of MPS may contribute to muscle loss with inactivity in older persons.