Merrick B Alex
National Center for Toxicogenomics, National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709, USA.
Brief Funct Genomic Proteomic. 2008 Jan;7(1):35-49. doi: 10.1093/bfgp/eln004. Epub 2008 Feb 12.
Toxicoproteomics uses the discovery potential of proteomics in toxicology research by applying global protein measurement technologies to biofluids and tissues after host exposure to injurious agents. Toxicoproteomic studies thus far have focused on protein profiling of major organs and biofluids such as liver and blood in preclinical species exposed to model toxicants. The slow pace of discovery for new biomarkers, toxicity signatures and mechanistic insights is partially due to the limited proteome coverage derived from analysis of native organs, tissues and body fluids by traditional proteomic platforms. Improved toxicoproteomic analysis would result by combining higher data density LC-MS/MS platforms with stable isotope labelled peptides and parallel use of complementary platforms. Study designs that remove abundant proteins from biofluids, enrich subcellular structures and include cell specific isolation from heterogeneous tissues would greatly increase differential expression capabilities. By leveraging resources from immunology, cell biology and nutrition research communities, toxicoproteomics could make particular contributions in three inter-related areas to advance mechanistic insights and biomarker development: the plasma proteome and circulating microparticles, the adductome and idiosyncratic toxicity.
毒理蛋白质组学通过将整体蛋白质测量技术应用于宿主暴露于有害因子后的生物流体和组织，在毒理学研究中发挥蛋白质组学的发现潜力。迄今为止，毒理蛋白质组学研究主要集中在暴露于模型毒物的临床前物种的主要器官和生物流体（如肝脏和血液）的蛋白质谱分析上。新生物标志物、毒性特征和机制见解的发现速度缓慢，部分原因是传统蛋白质组学平台对天然器官、组织和体液进行分析时蛋白质组覆盖范围有限。将更高数据密度的液相色谱-串联质谱（LC-MS/MS）平台与稳定同位素标记肽相结合，并并行使用互补平台，将有助于改进毒理蛋白质组学分析。从生物流体中去除丰富蛋白质、富集亚细胞结构以及从异质组织中进行细胞特异性分离的研究设计，将大大提高差异表达分析能力。通过利用来自免疫学、细胞生物学和营养研究领域的资源，毒理蛋白质组学可以在三个相互关联的领域做出特殊贡献，以推进机制研究和生物标志物开发：血浆蛋白质组和循环微颗粒、加合物组和特异质性毒性。
