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首页> 外文期刊>Environmental Science & Technology >Peroxisome Proliferator-Activated Receptor γ is a Sensitive Target for Oil Sands Process-Affected Water: Effects on Adipogenesis and Identification of Ligands
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Peroxisome Proliferator-Activated Receptor γ is a Sensitive Target for Oil Sands Process-Affected Water: Effects on Adipogenesis and Identification of Ligands

机译：过氧化物酶体增殖物激活的受体γ是油砂工艺影响的水的敏感目标：对脂肪形成和配体鉴定的影响

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摘要

Identification of toxic components of complex mixtures is a challenge. Here, oil sands process-affected water (OSPW) was used as a case study to identify those toxic components with a known protein target. Organic chemicals in OSPW exhibited dose-dependent activation of peroxisome proliferator-activated receptor γ (PPARγ) at concentrations less than those currently in the environment (0.025X equivalent of full-strength OSPW), by use of a luciferase reporter gene assay. Activation of PPARγ-mediated adipogenesis by OSPW was confirmed in 3T3L1 preadipocytes, as evidenced by accumulation of lipids and up-regulation of AP2, LPL, and PPARγ gene expression after exposure to polar fractions of OSPW. Unexpectedly, the nonpolar fractions of OSPW inhibited differentiation of preadipocytes via activation of the Wnt signaling pathway. Organic chemicals in OSPW that were ligands of PPARγ were identified by use of a pull-down system combined with untargeted chemical analysis (PUCA), with a recombinant PPARγ protein. Thirty ligands of PPARγ were identified by use of the PUCA assay. High resolution MS~1 and MS~2 spectra were combined to predict the formulas or structures of a subset of ligands, and polyoxygenated or heteroatomic chemicals, especially hydroxylated carboxylic/sulfonic acids, were the major ligands of PPARγ.
机译：鉴定复杂混合物的有毒成分是一项挑战。在此，以油砂工艺影响的水（OSPW）为例，以鉴定具有已知蛋白质靶标的那些有毒成分。通过使用萤光素酶报告基因分析，OSPW中的有机化学物质在低于当前环境浓度（全强度OSPW的0.025倍当量）的浓度下，过氧化物酶体增殖物激活受体γ（PPARγ）的剂量依赖性激活。在3T3L1前脂肪细胞中已证实OSPW激活了PPARγ介导的脂肪生成，这通过暴露于OSPW极性组分后脂质的积累以及AP2，LPL和PPARγ基因表达的上调来证明。出乎意料的是，OSPW的非极性部分通过Wnt信号通路的激活抑制前脂肪细胞的分化。 OSPW中的有机化学物质是PPARγ的配体，是通过使用下拉系统与无目标化学分析（PUCA）结合的重组PPARγ蛋白进行鉴定的。通过使用PUCA测定法鉴定了三十种PPARγ配体。结合高分辨率的MS〜1和MS〜2光谱来预测配体子集的分子式或结构，多氧化或杂原子化学物质，尤其是羟基化的羧酸/磺酸是PPARγ的主要配体。

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  • 来源
    《Environmental Science & Technology》 |2016年第14期|7816-7824|共9页
  • 作者

    Hui Peng; Jianxian Sun; Hattan A. Alharbi; Paul D. Jones; John. P. Giesy; Steve Wiseman;

  • 作者单位

    Toxicology Centre, University of Saskatchewan, 44 Campus Drive, Saskatoon, Saskatchewan Canada, S7N 5B3;

    Toxicology Centre, University of Saskatchewan, 44 Campus Drive, Saskatoon, Saskatchewan Canada, S7N 5B3;

    Toxicology Centre, University of Saskatchewan, 44 Campus Drive, Saskatoon, Saskatchewan Canada, S7N 5B3;

    Toxicology Centre, University of Saskatchewan, 44 Campus Drive, Saskatoon, Saskatchewan Canada, S7N 5B3,School of Environment and Sustainability, 117 Science Place, Saskatoon, Saskatchewan Canada, S7N 5C8;

    Toxicology Centre, University of Saskatchewan, 44 Campus Drive, Saskatoon, Saskatchewan Canada, S7N 5B3,Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, Saskatchewan Canada S7N 5B3,Zoology Department, Center for Integrative Toxicology, Michigan State University, East Lansing, Michigan 48824, United States,State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, People's Republic of China,School of Biology, University of Hong Kong, Hong Kong, SAR China;

    Toxicology Centre, University of Saskatchewan, 44 Campus Drive, Saskatoon, Saskatchewan Canada, S7N 5B3;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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