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RAW264.7细胞中可与1,4-NQ-BC结合的蛋白及其功能信息挖掘

Proteins that can bind to 1,4-NQ-BC in RAW264.7 cells and their functional information mining

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【作者】 刘玥彤江宛谕张琼崔原杨佳玮王阳张海晨肖倩倩孟庆贺蒋建军郝卫东魏雪涛

【Author】 LIU Yue-tong;JIANG Wan-yu;ZHANG Qiong;CUI Yuan;YANG Jia-wei;WANG Yang;ZHANG Hai-chen;XIAO Qian-qian;MENG Qing-he;JIANG Jian-jun;HAO Wei-dong;WEI Xue-tao;Department of Toxicology, School of Public Health, Peking University;Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety;

【通讯作者】 魏雪涛;

【机构】 北京大学公共卫生学院毒理学系食品安全毒理学研究与评价北京市重点实验室

【摘要】 目的 空气污染是影响广泛的公共卫生问题之一,其中颗粒物对人体的健康损害一直是研究热点。探究颗粒物进入细胞后与哪些蛋白会发生包括物理作用和化学作用在内的直接作用,有助于阐明颗粒物引起细胞功能损伤的机制。方法 本研究改进了Dominic开发的用于定量研究纳米颗粒物蛋白质冠(protein corona)的实验方法,利用蛋白组学技术,筛选了二次颗粒物的典型代表1,4-萘醌-黑炭(1,4-NQ-BC)可直接结合的蛋白质,利用GO富集分析和KEGG富集分析探究了这些蛋白的可能功能。结果 本研究共筛选得到645个蛋白,通过对其STRING蛋白互作关系进行聚类分析得到10簇不同蛋白,发现1,4-NQ-BC直接结合的蛋白主要影响细胞内质网、肌动蛋白细胞骨架、剪接体、核质转运和核糖体等相关功能,并可能与神经退行性病变相关蛋白结合。结论 本研究可为进一步探究1,4-NQ-BC的损伤机制提供线索;为探索不同类型颗粒物造成细胞损伤的机制提供新的方法学研究技术。

【Abstract】 Objective Air pollution is one of the problems which affect the health of the population widely. The harm of particulate matter to human health has always been a research hotspot. Exploring which proteins directly interact, including physical and chemical interactions, with particulate matter, when it enters cells, helps to elucidate the mechanism of damage on cellular function caused by particulate matter. Methods This study improved the experimental method, which was developed by Dominic for quantitative study of nanoparticle protein corona. Proteomics technology was used to excavate the effect of 1,4-Naphthoquinone Black Carbon(1,4-NQ-BC), a typical representative of secondary particulate matter, on macrophages. Possible functions were explored using GO enrichment analysis and KEGG enrichment analysis. Results Among all proteins detected by LC-MS, 645 proteins were selected which could be classified into 10 different clusters through cluster analysis depending on their STRING protein interactions in this study. It was found that the proteins directly adsorbed by 1,4-NQ-BC mainly affected the functions of the endoplasmic reticulum, actin cytoskeleton, spliceosomes, nucleocytoplasmic transport, ribosomes, and may be related to neurodegenerative diseases. Conclusion This study can provide clues for further exploring the damage mechanism of 1,4-NQ-BC. And it provided new methodological research techniques for researches on the mechanisms of cell damage caused by different types of particulate matter.

【基金】 国家自然科学基金(82173470)
  • 【文献出处】 毒理学杂志 ,Journal of Toxicology , 编辑部邮箱 ,2024年02期
  • 【分类号】R12
  • 【下载频次】9
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