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首页> 外文期刊>Environmental Science & Technology >Assessment of the Binding of Hydroxylated Polybrominated Diphenyl Ethers to Thyroid Hormone Transport Proteins Using a Site-Specific Fluorescence Probe
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Assessment of the Binding of Hydroxylated Polybrominated Diphenyl Ethers to Thyroid Hormone Transport Proteins Using a Site-Specific Fluorescence Probe

机译：使用位点特异性荧光探针评估羟基化的多溴联苯醚与甲状腺激素转运蛋白的结合

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摘要

Polybrominated diphenyl ethers (PBDEs) have been shown to disrupt thyroid hormone (TH) functions on experimental animals, and one of the proposed disruption mechanisms is the competitive binding of PBDE metabolites to TH transport proteins. In this report, a nonradioactive, site-specific fluorescein-thyroxine (F-T4) conjugate was designed and synthesized as a fluorescence probe to study the binding interaction of hydroxylated PBDEs to thyroxine-binding globulin (TBG) and transthyretin (TTR), two major TH transport proteins in human plasma. Compared with free F-T4, the fluorescence intensity of TTR-bound conjugate was enhanced by as much as 2-fold, and the fluorescence polarization value of TBG-bound conjugate increased by more than 20-fold These changes provide signal modulation mechanisms for F-T4 as a fluorescence probe. Based on fluorescence quantum yield and lifetime measurements, the fluorescence intensity enhancement was likely due to the elimination of intramolecular fluorescence quenching of fluorescein by T4 after F-T4 was bound to TTR. In circular dichroism and intrinsic tryptophan fluorescence measurements, F-T4 induced similar spectroscopic changes of the proteins as T4 did, suggesting that F-T4 bound to the proteins at the T4 binding site. By using F-T4 as the fluorescence probe in competitive binding assays, 11 OH-PBDEs with different levels of bromination and different hydroxylation positions were assessed for their binding affinity with TBG and TTR, respectively. The results indicate that the binding affinity generally increased with bromine number and OH position also played an important role. 3-OH-BDE-47 and 3-OH-BDE-154 bound to TTR and TBG even stronger, respectively, than T4. With rising environmental level and high bioaccumulation capability, PBDEs have the potential to disrupt thyroid homeostasis by competitive binding with TH transport proteins.
机译：多溴二苯醚（PBDEs）已显示破坏实验动物的甲状腺激素（TH）功能，并且提出的破坏机制之一是PBDE代谢物与TH转运蛋白的竞争结合。在本报告中，设计并合成了一种非放射性，位点特异性的荧光素-甲状腺素（F-T4）共轭物，以研究羟基化PBDEs与甲状腺素结合球蛋白（TBG）和运甲状腺素蛋白（TTR）的结合相互作用，两个人血浆中主要的TH转运蛋白。与游离F-T4相比，TTR结合的缀合物的荧光强度提高了2倍，TBG结合的缀合物的荧光偏振值增加了20倍以上。这些变化为F提供了信号调制机制。 -T4作为荧光探针。根据荧光量子产率和寿命测量，荧光强度的增强很可能是由于F-T4与TTR结合后T4消除了荧光素的分子内荧光猝灭作用。在圆二色性和固有色氨酸荧光测量中，F-T4诱导了与T4相似的蛋白质光谱变化，这表明F-T4在T4结合位点与蛋白质结合。通过在竞争性结合测定中使用F-T4作为荧光探针，分别评估了11种具有不同溴化水平和不同羟基化位置的OH-PBDEs与TBG和TTR的结合亲和力。结果表明，结合亲和力通常随溴数和OH位置而增加，也起重要作用。与TTR和TBG结合的3-OH-BDE-47和3-OH-BDE-154分别比T4强。随着环境水平的提高和高生物蓄积能力，PBDEs具有通过与TH转运蛋白竞争结合来破坏甲状腺稳态的潜力。

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  • 来源
    《Environmental Science & Technology》 |2012年第8期|p.4633-4640|共8页
  • 作者

    Xiao M. Ren; Liang-Hong Guo;

  • 作者单位

    State Key Laboratory of Environmental Chemistry and Eco-toxicology, Research Centre for Eco-environmental Sciences, Chinese Academy of Sciences, 18 Shuangqing Road, P.O. Box 2871, Beijing 100085, China;

    State Key Laboratory of Environmental Chemistry and Eco-toxicology, Research Centre for Eco-environmental Sciences, Chinese Academy of Sciences, 18 Shuangqing Road, P.O. Box 2871, Beijing 100085, China;

  • 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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