Quantitative iTRAQ-based proteomic analysis of differentially expressed proteins in aging in human and monkey
Quantitative iTRAQ-based proteomic analysis of differentially expressed proteins in aging in human and monkey
复制标题
基于 iTRAQ 的蛋白质组学分析，对人类和猴子衰老过程中差异表达的蛋白质进行定量分析
DOI：
10.1186/s12864-019-6089-z
复制
发表时间：
2019-10-11
期刊：
影响因子：
4.4
通讯作者：
Zhou, Yongxin
中科院分区：
文献类型：
--
作者：
Wang, Hao;Zhu, Xiaoqi;Zhou, Yongxin
背景与衰老相关的生理机制仍然是复杂和不清楚的。循环系统作为人体非常重要的组织，在衰老过程中也起着非常重要的作用。在这项研究中，我们使用同量异位素标签的相对和绝对定量（iTRAQ）的方法来确定差异表达的蛋白质在年轻和老年人和猴子的血浆。Western blotting和小鼠行为学实验对候选蛋白的表达进行了验证。结果在青年/老年人和青年/老年猴之间分别发现74和69个蛋白质的差异表达。在人类样本中，有38个蛋白质表达上调，36个蛋白质表达下调（变化倍数≥1.3或≤ 0.667，p值≤0.05）;在猴样本中，有51个蛋白质表达上调，18个蛋白质表达下调（变化倍数≥1.3或≤ 0.667，p值≤0.05）。KEGG通路分析显示，吞噬体、粘着斑、ECM-受体相互作用和PI 3 K/AKT信号通路是衰老过程中最常见的通路。在老年人和猴中均发现IGFBP 4蛋白表达上调。此外，通过Western印迹分析验证了IGFBP 4的差异表达，IGFBP 4治疗模拟了小鼠衰老相关的认知功能障碍。结论首先，对人和猴血浆蛋白进行整合蛋白质组学研究，发现IGFBP 4蛋白质具有促进衰老的作用。而且，iTRAQ分析表明，蛋白水解系统和炎症反应在衰老过程中起着重要作用。这些发现为更好地理解衰老的潜在机制提供了基础。
BackgroundThe underlying physiological mechanisms associated with aging are still complex and unclear. As a very important tissue of human body, the circulatory system also plays a very important role in the process of aging. In this study, we use the isobaric tags for relative and absolute quantification (iTRAQ) method to identify differentially expressed proteins in plasma for humans and monkeys between young and aged. Western blotting and behavioral experiment in mice were performed to validate the expression of the candidate protein.ResultsBetween the young / the old humans and the young / the old monkeys 74 and 69 proteins were found to be differently expressed, respectively. For the human samples, these included 38 up-regulated proteins and 36 down-regulated proteins (a fold change ≥1.3 or ≤ 0.667,pvalue ≤0.05).For the monkey samples, 51 up-regulated proteins and 18 down-regulated proteins (a fold change ≥1.3 or ≤ 0.667,pvalue ≤0.05). KEGG pathway analysis revealed that phagosome, focal adhesion, ECM-receptor interaction and PI3K/AKT signaling pathway were the most common pathways involved in aging. We found only IGFBP4 protein that existed in up-regulated proteins in aged both for human and monkey. In addition, the differential expression of IGFBP4 was validated by western blot analysis and IGFBP4 treatment mimicked aging-related cognitive dysfunction in mice.ConclusionsThis first, the integrated proteomics for the plasma protein of human and monkey reveal one protein-IGFBP4, which was validated by western blotting and behavioral analysis can promote the process of aging. And, iTRAQ analysis showed that proteolytic systems, and inflammatory responses plays an important role in the process of aging. These findings provide a basis for better understanding of the underlying mechanisms involved in aging.