Rapid upregulation and clearance of distinct circulating microRNAs after prolonged aerobic exercise
Rapid upregulation and clearance of distinct circulating microRNAs after prolonged aerobic exercise
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DOI：
10.1152/japplphysiol.01141.2013
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发表时间：
2014-03-01
影响因子：
3.3
通讯作者：
Chan, Stephen Y.
中科院分区：
文献类型：
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作者：
Baggish, Aaron L.;Park, Joseph;Chan, Stephen Y.
短的非蛋白质编码的RNA分子，称为microRNAs(MiRNAs)，是适应性过程的细胞内介质，包括肌肉肥大、收缩力量的产生和炎症。在基础状态和组织损伤期间，miRNAs以“循环”miRNAs(c-miRNAs)的形式释放到血液中。到目前为止，持续时间较长的次极量有氧运动对血浆c-miRNAs浓度的影响仍未完全确定。我们假设特定的c-miRNAs在长时间的有氧运动后有不同程度的上调。为了验证这一假设，我们测量了健康男性马拉松运动员(N=21)在安静时、马拉松结束后立即(42公里步行比赛)和比赛结束后24小时的c-miRNAs浓度，这些c-miRNAs富含肌肉(miR-1，miR-133a，miR-499-5p)、心脏组织(miR-208a)和血管内皮(miR-126)，以及那些与炎症有关的重要物质(miR-146a)。此外，我们将c-miRNA图谱与反映骨骼肌损伤、心脏应激和坏死以及全身炎症的传统蛋白质生物标志物进行了比较。候选c-miRNAs在马拉松比赛后立即增加，并在比赛完成24小时后下降到赛前水平或更低。然而，即使来自相同的组织类型，每个c-miRNA的变化幅度也不同。相比之下，传统的生物标志物在运动后有所增加，但在运动后24小时仍处于升高状态。因此，c-miRNAs对长时间运动的反应是不同的，这表明c-miRNA释放和清除的特定机制的存在不能完全用普遍的细胞损伤来解释。此外，c-miRNA的表达模式在时间上不同于传统的组织特异性生物标记物，强调了c-miRNAs作为运动诱导的组织适应的独特的实时标记物的潜力。
Short nonprotein coding RNA molecules, known as microRNAs (miRNAs), are intracellular mediators of adaptive processes, including muscle hypertrophy, contractile force generation, and inflammation. During basal conditions and tissue injury, miRNAs are released into the bloodstream as "circulating" miRNAs (c-miRNAs). To date, the impact of extended-duration, submaximal aerobic exercise on plasma concentrations of c-miRNAs remains incompletely characterized. We hypothesized that specific c-miRNAs are differentially upregulated following prolonged aerobic exercise. To test this hypothesis, we measured concentrations of c-miRNAs enriched in muscle (miR-1, miR-133a, miR-499-5p), cardiac tissue (miR-208a), and the vascular endothelium (miR-126), as well as those important in inflammation (miR-146a) in healthy male marathon runners (N = 21) at rest, immediately after a marathon (42-km foot race), and 24 h after the race. In addition, we compared c-miRNA profiles to those of conventional protein biomarkers reflective of skeletal muscle damage, cardiac stress and necrosis, and systemic inflammation. Candidate c-miRNAs increased immediately after the marathon and declined to prerace levels or lower after 24 h of race completion. However, the magnitude of change for each c-miRNA differed, even when originating from the same tissue type. In contrast, traditional biomarkers increased after exercise but remained elevated 24 h postexercise. Thus c-miRNAs respond differentially to prolonged exercise, suggesting the existence of specific mechanisms of c-miRNA release and clearance not fully explained by generalized cellular injury. Furthermore, c-miRNA expression patterns differ in a temporal fashion from corollary conventional tissue-specific biomarkers, emphasizing the potential of c-miRNAs as unique, real-time markers of exercise-induced tissue adaptation.