The impact of endurance exercise on global and AMPK gene-specific DNA methylation.
The impact of endurance exercise on global and AMPK gene-specific DNA methylation.
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DOI：
10.1016/j.bbrc.2016.04.078
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发表时间：
2016-05
影响因子：
3.1
通讯作者：
Tanya S. King-Himmelreich;Stefanie Schramm;Miriam C. Wolters;Julia Schmetzer;Christine V. Möser;Claudia Knothe;E. Resch;Johannes Peil;G. Geisslinger;E. Niederberger
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文献类型：
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作者：
Tanya S. King-Himmelreich;Stefanie Schramm;Miriam C. Wolters;Julia Schmetzer;Christine V. Möser;Claudia Knothe;E. Resch;Johannes Peil;G. Geisslinger;E. Niederberger
经常描述基因表达的改变作为体育锻炼的结果。这些调控机制可能依赖于全局或基因特异性DNA甲基化水平的表观遗传变化。AMP活化蛋白激酶（AMPK）在维持能量稳态中起关键作用，并且通过运动活动后骨骼肌中发生的AMP/ATP比率的增加而活化。为了分析运动是否对AMPK启动子的甲基化状态有影响，我们测定了康复背景下运动活动前后患者血液样本以及训练和未训练小鼠骨骼肌中AMPK甲基化状态。此外，我们检测了长散布核元件1（LINE-1）作为整体DNA甲基化变化的指标，结果表明，小鼠和人类的轻度运动活动不会改变整体DNA甲基化，但会影响AMPK α 2基因中特定CpG位点的甲基化。这些结果表明，运动对人血液和小鼠骨骼肌AMPK α 2基因甲基化有显著影响，因此可能抑制AMPK α 2基因的表达。
Alterations in gene expression as a consequence of physical exercise are frequently described. The mechanism of these regulations might depend on epigenetic changes in global or gene-specific DNA methylation levels. The AMP-activated protein kinase (AMPK) plays a key role in maintenance of energy homeostasis and is activated by increases in the AMP/ATP ratio as occurring in skeletal muscles after sporting activity. To analyze whether exercise has an impact on the methylation status of theAMPKpromoter, we determined theAMPKmethylation status in human blood samples from patients before and after sporting activity in the context of rehabilitation as well as in skeletal muscles of trained and untrained mice. Further, we examined long interspersed nuclear element 1 (LINE-1) as indicator of global DNA methylation changes.Our results revealed that light sporting activity in mice and humans does not alter global DNA methylation but has an effect on methylation of specific CpG sites in theAMPKα2gene. These regulations were associated with a reduced AMPKα2 mRNA and protein expression in muscle tissue, pointing at a contribution of the methylation status toAMPKexpression.Taken together, these results suggest that exercise influencesAMPKα2gene methylation in human blood and eminently in the skeletal muscle of mice and therefore might repressAMPKα2gene expression.