Center of Excellence for Proteomics, Division of Systems Biology, National Center for Toxicological Research, FDA, Jefferson, AR 72079, USA.
J Proteomics. 2011 Nov 18;74(12):2745-59. doi: 10.1016/j.jprot.2011.08.009. Epub 2011 Aug 22.
Human exposure to nanoparticles is inevitable from natural and anthropogenic sources. Titanium dioxide (TiO2) nanoparticles are increasingly being used in pharmaceutical and cosmetic products. Previous studies revealed that TiO2 levels were significantly increased in tissues (e.g., lymph nodes) after mice were injected with nanosized TiO2. To identify early response lymph node proteins to TiO2 nanoparticles, groups of mice were intradermally injected with a low dose of DeGussa P25 TiO2 nanoparticles or vehicle alone. The proteomes of lymph nodes at 24 h were quantitatively analyzed using trypsin-catalyzed 16O/18O labeling in conjunction with two-dimensional liquid chromatography separation and tandem mass spectrometry (2DLC-MS/MS). A total of 33 proteins were significantly changed (over 1.3-fold, p<0.05) in the mice treated with TiO2 nanoparticles, which accounted for approximately 1% of the total proteins identified. The differentially expressed proteins mainly involve the immune response (e.g., inflammation), lipid and fatty acid metabolism, mRNA processing, and nucleosome assembly. Regulation of functionally distinct classes of proteins could be mediated by estrogen receptor (ESR1), PPARγ, and c-Myc signalings, etc. The differentially expressed proteins identified in this experiment could represent early response proteins to TiO2 nanoparticle treatment in mouse lymph nodes.
人类不可避免地会从自然和人为来源接触到纳米颗粒。二氧化钛(TiO2)纳米颗粒越来越多地被用于制药和化妆品产品。以前的研究表明,在给小鼠注射纳米 TiO2 后,组织(例如淋巴结)中的 TiO2 水平显著增加。为了鉴定 TiO2 纳米颗粒对早期反应淋巴结蛋白的影响,将小鼠分组并经皮注射低剂量的 Degussa P25 TiO2 纳米颗粒或单独的载体。使用胰蛋白酶催化的 16O/18O 标记结合二维液相色谱分离和串联质谱(2DLC-MS/MS)对 24 小时的淋巴结蛋白质组进行定量分析。在接受 TiO2 纳米颗粒处理的小鼠中,有 33 种蛋白质发生了显著变化(超过 1.3 倍,p<0.05),占鉴定出的总蛋白质的约 1%。差异表达的蛋白质主要涉及免疫反应(如炎症)、脂质和脂肪酸代谢、mRNA 处理和核小体组装。功能不同类别的蛋白质的调节可能由雌激素受体(ESR1)、PPARγ 和 c-Myc 信号等介导。本实验中鉴定的差异表达蛋白可能代表小鼠淋巴结对 TiO2 纳米颗粒处理的早期反应蛋白。