Laboratory for Ecophysiology, Biochemistry and Toxicology, Department of Biology, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium.
Gen Comp Endocrinol. 2010 Jun 1;167(2):190-201. doi: 10.1016/j.ygcen.2010.03.003. Epub 2010 Mar 18.
Nowadays there is much concern about the presence of endocrine disrupting compounds (EDCs) in the environment due to their ability to interfere with the endocrine system. In the presented study, adult zebrafish (Danio rerio) were exposed to 30 ng L(-1) 17alpha-ethinylestradiol (EE2) for 4 and 28 days. The underlying molecular mechanisms of EE2 were studied in the zebrafish liver by applying a combined transcriptomics and proteomics approach. In addition, we assessed the added value of such an integrated-omics approach. Oligo microarrays, spotted with 3479 zebrafish-specific oligos, were employed to generate differential gene expression levels. The proteomic responses were evaluated by means of differential in-gel electrophoresis (DiGE), combined with MALDI-tandem mass spectrometry. Assessment of the major biological functions of the differentially expressed transcripts and proteins illustrated that both individual platforms could profile a clear estrogenic interference, next to numerous metabolism-related effects and stress responses. Cross-comparison of both transcriptomics and proteomics datasets displayed limited concordance, though, thorough revision of the results illustrated that transcriptional effects were projected on protein level as downstream effects of affected signalling pathways. Overall, this study demonstrated that a proteomics approach can lift the biological interpretation of microarrays to a higher level, and moreover, opens a window for identification of possible new biomarkers.
如今,由于内分泌干扰化合物 (EDCs) 能够干扰内分泌系统,因此人们非常关注它们在环境中的存在。在本研究中,成年斑马鱼 (Danio rerio) 暴露于 30ng/L-1 的 17alpha-乙炔基雌二醇 (EE2) 中 4 天和 28 天。通过应用转录组学和蛋白质组学相结合的方法,研究了 EE2 在斑马鱼肝脏中的潜在分子机制。此外,我们评估了这种集成组学方法的附加值。使用 3479 个斑马鱼特异性寡核苷酸点样的寡微阵列生成差异基因表达水平。通过差异凝胶电泳 (DiGE) 与 MALDI-串联质谱相结合评估蛋白质组学反应。评估差异表达的转录物和蛋白质的主要生物学功能表明,两种平台都可以清楚地分析雌激素干扰,除了许多代谢相关的影响和应激反应。尽管对两种转录组学和蛋白质组学数据集进行交叉比较显示出有限的一致性,但对结果的深入审查表明,转录效应是受影响的信号通路的下游效应在蛋白质水平上的投影。总的来说,这项研究表明蛋白质组学方法可以将微阵列的生物学解释提升到更高的水平,并且还为鉴定可能的新生物标志物开辟了道路。