Proteome profiling reveals potential toxicity and detoxification pathways following exposure of BEAS-2B cells to engineered nanoparticle titanium dioxide
Proteome profiling reveals potential toxicity and detoxification pathways following exposure of BEAS-2B cells to engineered nanoparticle titanium dioxide
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DOI：
10.1002/pmic.201000741
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发表时间：
2011-06-01
期刊：
影响因子：
3.4
通讯作者：
Prasad, Raju Y.
中科院分区：
文献类型：
--
作者：
Ge, Yue;Bruno, Maribel;Prasad, Raju Y.
已知氧化应激在工程纳米材料诱导的细胞毒性中起重要作用。然而，与工程纳米材料介导的氧化应激和毒性相关的蛋白质和信号通路在很大程度上是未知的。为了确定与暴露于工程纳米材料相关的这些毒性途径和网络，使用人支气管上皮细胞、BEAS-2B和纳米级二氧化钛进行了综合蛋白质组学研究。利用2-DE和MS，我们确定了46个蛋白质，改变了蛋白质表达水平。2-DE/MS检测到的蛋白质变化通过功能蛋白分析进行验证。这些蛋白质包括参与细胞应激反应、代谢、粘附、细胞骨架动力学、细胞生长、细胞死亡和细胞信号传导的关键蛋白质。差异表达的蛋白质使用Insufficiency Pathway Analyses（TM）的经典途径和Insufficiency Pathway Analyses tox list进行定位，以创建蛋白质相互作用网络和蛋白质组学途径。生成了20种蛋白质经典途径和毒性列表，并将这些途径与用二氧化钛处理的BEAS-2B细胞的基因组分析生成的信号传导途径进行比较。从蛋白质组学和基因组学数据产生的特定途径和列表中存在显著重叠。此外，我们还分析了二氧化钛处理的BEAS-2B细胞中蛋白激酶的磷酸化谱，以更好地理解响应于二氧化钛处理和诱导的氧化应激的上游信号通路。总之，本研究提供了第一个蛋白质相互作用网络图和新的见解的生物反应和潜在的毒性和解毒途径的二氧化钛。
Oxidative stress is known to play important roles in engineered nanomaterial-induced cellular toxicity. However, the proteins and signaling pathways associated with the engineered nanomaterial-mediated oxidative stress and toxicity are largely unknown. To identify these toxicity pathways and networks that are associated with exposure to engineered nanomaterials, an integrated proteomic study was conducted using human bronchial epithelial cells, BEAS-2B and nanoscale titanium dioxide. Utilizing 2-DE and MS, we identified 46 proteins that were altered at protein expression levels. The protein changes detected by 2-DE/MS were verified by functional protein assays. These identified proteins include some key proteins involved in cellular stress response, metabolism, adhesion, cytoskeletal dynamics, cell growth, cell death, and cell signaling. The differentially expressed proteins weremapped using Ingenuity Pathway Analyses (TM) canonical pathways and Ingenuity Pathway Analyses tox lists to create protein-interacting networks and proteomic pathways. Twenty protein canonical pathways and tox lists were generated, and these pathways were compared to signaling pathways generated from genomic analyses of BEAS-2B cells treated with titanium dioxide. There was a significant overlap in the specific pathways and lists generated from the proteomic and the genomic data. In addition, we also analyzed the phosphorylation profiles of protein kinases in titanium dioxide-treated BEAS-2B cells for a better understanding of upstream signaling pathways in response to the titanium dioxide treatment and the induced oxidative stress. In summary, the present study provides the first protein-interacting network maps and novel insights into the biological responses and potential toxicity and detoxification pathways of titanium dioxide.