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鉴定受 PCB 污染牛体内暴露的候选生物标志物:基于基因表达和蛋白质组学的方法。

Identification of candidate biomarkers of the exposure to PCBs in contaminated cattle: A gene expression- and proteomic-based approach.

机构信息

Department of Veterinary Sciences, University of Torino, Largo P. Braccini 2, Grugliasco, Italy.

Proteomics and Mass Spectrometry Laboratory, ISPAAM, National Research Council, Via Argine 1085, Napoli, Italy.

出版信息

Sci Total Environ. 2018 Nov 1;640-641:22-30. doi: 10.1016/j.scitotenv.2018.05.284. Epub 2018 May 28.

DOI:10.1016/j.scitotenv.2018.05.284
PMID:29852444
Abstract

Dioxins and polychlorinated biphenyls (PCBs) are widespread and persistent contaminants. Through a combined gene expression/proteomic-based approach, candidate biomarkers of the exposure to such environmental pollutants in cattle subjected to a real eco-contamination event were identified. Animals were removed from the polluted area and fed a standard ration for 6 months. The decontamination was monitored by evaluating dioxin and PCB levels in pericaudal fat two weeks after the removal from the contaminated area (day 0) and then bimonthly for six months (days 59, 125 and 188). Gene expression measurements demonstrated that CYP1B1 expression was significantly higher in blood lymphocytes collected in contaminated animals (day 0), and decreased over time during decontamination. mRNA levels of interleukin 2 showed an opposite quantitative trend. MALDI-TOF-MS polypeptide profiling of serum samples ascertained a progressive decrease (from day 0 to 188) of serum levels of fibrinogen β-chain and serpin A3-7-like fragments, apolipoprotein (APO) C-II and serum amyloid A-4 protein, along with an augmented representation of transthyretin isoforms, as well as APOC-III and APOA-II proteins during decontamination. When differentially represented species were combined with serum antioxidant, acute phase and proinflammatory protein levels already ascertained in the same animals (Cigliano et al., 2016), bioinformatics unveiled an interaction network linking together almost all components. This suggests the occurrence of a complex PCB-responsive mechanism associated with animal contamination/decontamination, including a cohort of protein/polypeptide species involved in blood redox homeostasis, inflammation and lipid transport. All together, these results suggest the use in combination of such biomarkers for identifying PCB-contaminated animals, and for monitoring the restoring of their healthy condition following a decontamination process.

摘要

二恶英和多氯联苯(PCBs)是广泛存在且持久的污染物。通过结合基因表达/蛋白质组学方法,确定了在经历真实生态污染事件的牛中,用于此类环境污染物暴露的候选生物标志物。动物被从污染区域移走,并在 6 个月内喂食标准饮食。通过在从污染区域移除后两周(第 0 天)评估尾侧脂肪中的二恶英和 PCB 水平,并在接下来的六个月内每两个月监测一次(第 59、125 和 188 天)来监测去污染情况。基因表达测量表明,在受污染动物的血液淋巴细胞中,CYP1B1 的表达在第 0 天明显更高,并在去污染过程中随时间降低。白细胞介素 2 的 mRNA 水平表现出相反的定量趋势。对血清样本的 MALDI-TOF-MS 多肽分析确定了血清纤维蛋白原β链和丝氨酸蛋白酶抑制剂 A3-7 样片段、载脂蛋白(APO)C-II 和血清淀粉样蛋白 A-4 蛋白的血清水平的逐渐降低(从第 0 天到 188 天),以及转甲状腺素蛋白同工型、APOC-III 和 APOA-II 蛋白的表达增加,在去污染过程中。当将差异表达的物种与同一动物中已经确定的血清抗氧化剂、急性期和促炎蛋白水平结合使用时(Cigliano 等人,2016 年),生物信息学揭示了一个将几乎所有成分联系在一起的相互作用网络。这表明存在与动物污染/去污染相关的复杂 PCB 反应机制,包括参与血液氧化还原稳态、炎症和脂质转运的蛋白质/多肽物种。所有这些结果表明,在识别 PCB 污染动物和监测其在去污染过程中恢复健康状态时,可以结合使用这些生物标志物。

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