BfR, German Federal Institute for Risk Assessment , Max-Dohrn-Str. 8-10, 10589 Berlin, Germany.
Technical University Berlin, ZE Electronmicroscopy , Straße des 17. Juni 135, 10623 Berlin, Germany.
J Proteome Res. 2017 Nov 3;16(11):4020-4034. doi: 10.1021/acs.jproteome.7b00412. Epub 2017 Oct 6.
The breadth of applications of nanoparticles and the access to food-associated consumer products containing nanosized materials lead to oral human exposure to such particles. In biological fluids nanoparticles dynamically interact with biomolecules and form a protein corona. Knowledge about the protein corona is of great interest for understanding the molecular effects of particles as well as their fate inside the human body. We used a mass spectrometry-based toxicoproteomics approach to elucidate mechanisms of toxicity of silver nanoparticles and to comprehensively characterize the protein corona formed around silver nanoparticles in Caco-2 human intestinal epithelial cells. Results were compared with respect to the cellular function of proteins either affected by exposure to nanoparticles or present in the protein corona. A transcriptomic data set was included in the analyses in order to obtain a combined multiomics view of nanoparticle-affected cellular processes. A relationship between corona proteins and the proteomic or transcriptomic responses was revealed, showing that differentially regulated proteins or transcripts were engaged in the same cellular signaling pathways. Protein corona analyses of nanoparticles in cells might therefore help in obtaining information about the molecular consequences of nanoparticle treatment.
纳米颗粒的应用范围广泛,人们可以接触到含有纳米材料的食品相关消费品,从而导致经口摄入纳米颗粒。在生物流体中,纳米颗粒会与生物分子动态相互作用,并形成蛋白质外壳。了解蛋白质外壳对于理解颗粒的分子效应及其在人体内的命运具有重要意义。我们使用基于质谱的毒理学蛋白质组学方法来阐明银纳米颗粒的毒性作用机制,并全面描述在 Caco-2 人肠上皮细胞中形成的银纳米颗粒的蛋白质外壳。我们比较了暴露于纳米颗粒后受影响的蛋白质的细胞功能与存在于蛋白质外壳中的蛋白质的细胞功能。为了获得受纳米颗粒影响的细胞过程的综合多组学观点,我们将转录组数据集纳入了分析。结果揭示了蛋白质外壳与蛋白质组学或转录组学反应之间的关系,表明差异调节的蛋白质或转录本参与了相同的细胞信号通路。因此,对细胞中纳米颗粒的蛋白质外壳进行分析,可能有助于获取有关纳米颗粒处理的分子后果的信息。