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长期适度运动增强构成神经营养因子信号通路的特定蛋白质:基于 TMT 的大鼠血浆定量蛋白质组学分析。

Long-term moderate exercise enhances specific proteins that constitute neurotrophin signaling pathway: A TMT-based quantitative proteomic analysis of rat plasma.

机构信息

Center for Scientific Research and Institute of Exercise and Health, Guangzhou Sports University, Guangzhou 510500, China.

Institute of Neuroscience and the Second Affiliated Hospital, Guangzhou Medical University, Guangzhou 510260, China.

出版信息

J Proteomics. 2018 Aug 15;185:39-50. doi: 10.1016/j.jprot.2018.06.017. Epub 2018 Jun 25.

DOI:10.1016/j.jprot.2018.06.017
PMID:29953961
Abstract

UNLABELLED

Physical exercise has been reported to increase neurotrophin in brain tissues as hippocampus as well as increased neurotrophic level peripherally in blood plasma and might have an effect on/or affect molecular processes of energy metabolism (and homeostasis). In this study, using quantitative proteomic analysis, we obtained a plasma protein profile from the rat with long-term moderate exercise. A total of 752 proteins were identified in the plasma. Among them, 54 proteins were significant up-regulated and 47 proteins were down-regulated in the plasma of exercise group compared with the control group. Bioinformatic analyses showed that these altered proteins are widely involved in multiple biological processes, molecular functions and cellular components, which connect with 11 signaling pathways. Interestingly, 5 up-regulated proteins Rap1b, PTPN11, ARHGDIA, Cdc42 and YWHAE, confirmed by Western blots, are involved in the neurotrophin signaling pathway which shows the lowest P value among the identified pathways. Further analyses showed that the 5 neurotrophin-signaling-pathway-related proteins participate in two important protein-protein interaction networks associated to cell survival and apoptosis, axonal development, synapse formation and plasticity. This study provides an exercise-induced plasma protein profile, suggesting that long-term exercise enhances the proteins involved in neurotrophin signaling pathway which may contribute to health benefit.

SIGNIFICANCE

Physical activity contributes to myriad benefits on body health across the lifespan. The changes in plasma proteins after chronic moderate exercise may be used as biomarkers for health and may also play important roles in increase of cardiovascular fitness, enhancement of immune competence, prevention of obesity, decrease of risk for neurological disorders, cancer, stroke, diabetes and other metabolic disorders. Using a TMT-based proteomic method, this study identified 101 altered proteins in the plasma of rats after long-term moderate treadmill running, which may provide novel biomarkers for further investigation of the underlying mechanism of physical exercise. We confirmed that exercise enhances 5 proteins of the neurotrophin signaling pathway that may contribute to health benefits.

摘要

未加标签

有报道称,体育锻炼可增加大脑组织(如海马体)中的神经营养因子,并在外周血液血浆中增加神经营养因子水平,可能对/影响能量代谢(和动态平衡)的分子过程。在这项研究中,我们使用定量蛋白质组学分析方法,从长期进行中度运动的大鼠中获得了血浆蛋白图谱。在血浆中总共鉴定出 752 种蛋白质。其中,与对照组相比,运动组的血浆中有 54 种蛋白显著上调,47 种蛋白下调。生物信息学分析表明,这些改变的蛋白广泛参与多种生物学过程、分子功能和细胞成分,与 11 种信号通路相连。有趣的是,通过 Western blot 验证的 5 种上调蛋白 Rap1b、PTPN11、ARHGDIA、Cdc42 和 YWHAE,参与了神经生长因子信号通路,该通路是所鉴定通路中 P 值最低的通路。进一步分析表明,这 5 种神经生长因子信号通路相关蛋白参与了与细胞存活和凋亡、轴突发育、突触形成和可塑性相关的两个重要蛋白质-蛋白质相互作用网络。本研究提供了一个运动诱导的血浆蛋白图谱,表明长期运动增强了神经生长因子信号通路相关蛋白,这可能有助于健康获益。

意义

身体活动对整个生命周期的身体健康有无数益处。慢性中度运动后血浆蛋白的变化可作为健康的生物标志物,也可能在增加心血管健康、增强免疫能力、预防肥胖、降低患神经紊乱、癌症、中风、糖尿病和其他代谢紊乱的风险方面发挥重要作用。本研究使用 TMT 蛋白质组学方法,鉴定出大鼠长期进行中度跑步机跑步后血浆中 101 种改变的蛋白,这些蛋白可能为进一步研究身体运动的潜在机制提供新的生物标志物。我们证实运动增强了神经生长因子信号通路的 5 种蛋白,这可能有助于健康获益。

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