Analysis of global mRNA expression in human skeletal muscle during recovery from endurance exercise

Analysis of global mRNA expression in human skeletal muscle during recovery from endurance exercise
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DOI:
10.1096/fj.04-3149fje
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发表时间:
2005-06-01
期刊:
影响因子:
4.8
通讯作者:
Tarnopolsky, MA
Tarnopolsky, MA
中科院分区:
生物学2区
文献类型:
--
作者:
Mahoney, DJ;Parise, G;Tarnopolsky, MA

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为了寻找耐力运动后骨骼肌中激活的新型转录途径,我们使用cDNA微阵列来测量高强度循环(类似于75分钟)后的全局mRNA表达。健康、年轻、久坐不动的男性进行了自行车比赛,并在运动前、运动后3小时和48小时从股外侧肌进行了骨骼肌活检。我们使用cDNA微阵列检测了四名受试者的单个肌肉样本中的mRNA表达,使用重复测量的微阵列显著性分析(SAM)来确定具有统计学意义的表达变化,并使用实时RT-PCR证实了所选结果。共有118个基因在循环3 h后表达量显著增加,8个基因表达量显著降低。48 h时,29个基因表达量显著升高,5个基因表达量显著降低。其中许多是参与运动恢复和适应的潜在重要的新基因,包括一些参与1)代谢和线粒体生物发生的基因(FOXO1、PPAR δ、PPAR γ、核受体结合蛋白2、IL- 6受体、核糖体蛋白L2、氨基乙酰酸δ合酶2);2)氧化应激反应(金属硫蛋白1B、1F、1G、1H、1L、2A、3、干扰素调节因子1);3)电解质跨膜运输[Na+- K+- atp酶(β 3), SERCA3,氯通道4]。其他包括参与细胞应激、蛋白水解、凋亡、生长、分化和转录激活的基因,以及所有三个核受体亚家族4A家族成员(Nur77、Nurr1和Nor1)。这项研究首次表征了耐力运动后恢复过程中的全局mRNA表达,结果为以下方面提供了潜在的见解:1)耐力运动后人类骨骼肌稳态恢复的转录贡献,以及2)单次耐力运动对一段时间耐力运动训练后发生的适应性过程的转录贡献。
To search for novel transcriptional pathways that are activated in skeletal muscle after endurance exercise, we used cDNA microarrays to measure global mRNA expression after an exhaustive bout of high-intensity cycling (similar to 75 min). Healthy, young, sedentary males performed the cycling bout, and skeletal muscle biopsies were taken from the vastus lateralis before, and at 3 and 48 h after exercise. We examined mRNA expression in individual muscle samples from four subjects using cDNA microarrays, used repeated-measures significance analysis of microarray (SAM) to determine statistically significant expression changes, and confirmed selected results using real-time RT-PCR. In total, the expression of 118 genes significantly increased 3 h postcycling and 8 decreased. At 48 h, the expression of 29 genes significantly increased and 5 decreased. Many of these are potentially important novel genes involved in exercise recovery and adaptation, including several involved in 1) metabolism and mitochondrial biogenesis ( FOXO1, PPAR delta, PPAR gamma, nuclear receptor binding protein 2, IL- 6 receptor, ribosomal protein L2, aminolevulinate delta-synthase 2); 2) the oxidant stress response (metalothioneins 1B, 1F, 1G, 1H, 1L, 2A, 3, interferon regulatory factor 1); and 3) electrolyte transport across membranes [Na+- K+- ATPase (beta 3), SERCA3, chloride channel 4]. Others include genes involved in cell stress, proteolysis, apoptosis, growth, differentiation, and transcriptional activation, as well as all three nuclear receptor subfamily 4A family members (Nur77, Nurr1, and Nor1). This study is the first to characterize global mRNA expression during recovery from endurance exercise, and the results provide potential insight into 1) the transcriptional contributions to homeostatic recovery in human skeletal muscle after endurance exercise, and 2) the transcriptional contributions from a single bout of endurance exercise to the adaptive processes that occur after a period of endurance exercise training.