Cell-free DNA release under psychosocial and physical stress conditions.

Cell-free DNA release under psychosocial and physical stress conditions.
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DOI:
10.1038/s41398-018-0264-x
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发表时间:
2018-10-29
影响因子:
6.8
通讯作者:
Moser DA
Moser DA
中科院分区:
医学1区
文献类型:
--
作者:
Hummel EM;Hessas E;Müller S;Beiter T;Fisch M;Eibl A;Wolf OT;Giebel B;Platen P;Kumsta R;Moser DA

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将心理压力与疾病风险联系起来的机制的理解依赖于可靠的压力生物标志物。循环中的无细胞DNA(CfDNA)已成为细胞应激、衰老、炎症过程和细胞死亡的潜在生物标志物。最近的研究表明,心理社会压力和体育锻炼也可能影响它的释放。我们比较了急性心理社会和体育锻炼应激对cfDNA释放的影响,将20名年轻、健康的男性暴露在急性心理社会实验室应激源和急性体育锻炼应激源中。在应激暴露前后采集静脉血和唾液样本。从血浆中提取无细胞DNA,用定量聚合酶链式反应进行定量。此外,还分析了cfDNA片段长度,并分析了cfDNA甲基化模式。此外,还测量了应激激素的释放和主观应激反应。结果显示,TSST后cfDNA增加2倍,力竭运动后cfDNA增加5倍,力竭后cfDNA短小片段过多。有趣的是,在两种应激模式后,无细胞线粒体DNA显示出类似的增加。此外,cfDNA甲基化签名--这里用作不同细胞来源的标志--在压力测试后有显著不同。虽然DNA甲基化在心理社会应激后立即降低,但在物理应激后增加,这表明不同的细胞来源活跃的DNA释放。综上所述,我们的结果提示刺激和细胞特异性调节cfDNA的释放。虽然与应激相关的cfDNA释放的功能作用仍然难以捉摸,但它可能作为心理生理应激反应的一部分,在分子应激研究中作为一个有价值的生物标记物。
The understanding of mechanisms linking psychological stress to disease risk depend on reliable stress biomarkers. Circulating cell-free DNA (cfDNA) has emerged as a potential biomarker of cellular stress, aging, inflammatory processes, and cell death. Recent studies indicated that psychosocial stress and physical exercise might also influence its release. We compared the effects of acute psychosocial and physical exercise stress on cfDNA release by exposing 20 young, healthy men to both an acute psychosocial laboratory stressor and an acute physical exercise stressor. Venous blood and saliva samples were collected before and after stress exposure. Cell-free DNA was extracted from plasma and quantified by qPCR. Furthermore, cfDNA fragment length was analyzed and cfDNA methylation patterns were assayed across time. In addition, release of stress hormones and subjective stress responses were measured. Results showed a twofold increase of cfDNA after TSST and fivefold increase after exhaustive treadmill exercise, with an overabundance of shorter cfDNA fragments after physical exhaustion. Interestingly, cell-free mitochondrial DNA showed similar increase after both stress paradigms. Furthermore, cfDNA methylation signatures—used here as a marker for diverse cellular origin—were significantly different post stress tests. While DNA methylation decreased immediately after psychosocial stress, it increased after physical stress, suggesting different cellular sources of active DNA release. In summary, our results suggest stimulus and cell-specific regulation of cfDNA release. Whereas the functional role of stress-associated cfDNA release remains elusive, it might serve as a valuable biomarker in molecular stress research as a part of the psychophysiological stress response.
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期刊: Current biology : CB
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