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必需氨基酸增加 microRNA-499、-208b 和 -23a,并下调人骨骼肌中肌肉生长抑制素和肌细胞增强因子 2C mRNA 的表达。

Essential amino acids increase microRNA-499, -208b, and -23a and downregulate myostatin and myocyte enhancer factor 2C mRNA expression in human skeletal muscle.

机构信息

Department of Physical Therapy, Division of Rehabilitation Science, University of Texas Medical Branch, Galveston, TX 77555, USA.

出版信息

J Nutr. 2009 Dec;139(12):2279-84. doi: 10.3945/jn.109.112797. Epub 2009 Oct 14.

Abstract

Essential amino acids (EAA) stimulate muscle protein synthesis in humans. However, little is known about whether microRNAs (miRNA) and genes associated with muscle growth are expressed differently following EAA ingestion. Our purpose in this experiment was to determine whether miRNA and growth-related mRNA expressed in skeletal muscle are up- or downregulated in humans following the ingestion of EAA. We hypothesized that EAA would alter miRNA expression in skeletal muscle as well as select growth-related genes. Muscle biopsies were obtained from the vastus lateralis of 7 young adult participants (3 male, 4 female) before and 3 h after ingesting 10 g of EAA. Muscle samples were analyzed for muscle miRNA (miR-499, -208b, -23a, -1, -133a, and -206) and muscle-growth related genes [MyoD1, myogenin, myostatin, myocyte enhancer factor C (MEF2C), follistatin-like-1 (FSTL1), histone deacytylase 4, and serum response factor mRNA] before and after EAA ingestion using real-time PCR. Following EAA ingestion, miR-499, -208b, -23a, -1, and pri-miR-206 expression increased (P < 0.05). The muscle-growth genes MyoD1 and FSTL1 mRNA expression increased (P < 0.05), and myostatin and MEF2C mRNA were downregulated following EAA ingestion (P < 0.05). We conclude that miRNA and growth-related genes expressed in skeletal muscle are rapidly altered within hours following EAA ingestion. Further work is needed to determine whether these miRNA are post-transcriptional regulators of growth-related genes following an anabolic stimulus.

摘要

必需氨基酸(EAA)可刺激人体的肌肉蛋白合成。然而,人们对于 EAA 摄入后,与肌肉生长相关的 miRNA 和基因是否会表现出不同的表达知之甚少。我们的实验目的是确定 EAA 摄入后骨骼肌中的 miRNA 和与生长相关的 mRNA 是否会被上调或下调。我们假设 EAA 会改变骨骼肌中的 miRNA 表达以及某些与生长相关的基因。在摄入 10 克 EAA 之前和之后 3 小时,从 7 名年轻成年参与者(3 名男性,4 名女性)的股外侧肌中获取肌肉活检。使用实时 PCR 分析肌肉样本中的肌肉 miRNA(miR-499、-208b、-23a、-1、-133a 和 -206)和与肌肉生长相关的基因[MyoD1、myogenin、myostatin、myocyte enhancer factor C(MEF2C)、follistatin-like-1(FSTL1)、组蛋白去乙酰化酶 4 和血清反应因子 mRNA]在 EAA 摄入前后的表达情况。EAA 摄入后,miR-499、-208b、-23a、-1 和 pri-miR-206 的表达增加(P<0.05)。肌肉生长基因 MyoD1 和 FSTL1 的 mRNA 表达增加(P<0.05),而 myostatin 和 MEF2C 的 mRNA 则在 EAA 摄入后下调(P<0.05)。我们得出结论,EAA 摄入后数小时内,骨骼肌中的 miRNA 和与生长相关的基因表达迅速改变。需要进一步的研究来确定这些 miRNA 是否是合成代谢刺激后与生长相关的基因的转录后调节因子。

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