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首页> 外文期刊>Environmental Science & Technology >Measuring the Kinetics of the Binding of Xenoestrogens and Estrogen Receptor Alpha by Fluorescence Polarization
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Measuring the Kinetics of the Binding of Xenoestrogens and Estrogen Receptor Alpha by Fluorescence Polarization

机译：通过荧光偏振测量异雌激素和雌激素受体α结合的动力学。

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摘要

The mechanism of endocrine disruption by environmental xenoestrogens is unclear. Bisphenol-A (BPA) is an example. Its concentration in human serum is low, and its binding with estrogen receptor (ER) is weak. Yet its effect on prostate and mammary gland development was observed. We investigated whether this effect could be explained in terms of binding kinetics. We used the method of fluorescence polarization anisotropy to measure the kinetic rate constants of the binding of ERα with 19 xenoestrogens. Relative binding affinities (RBA) were also deduced from the kinetics. We drew three observations. First, our RBAs were consistent with published values, thus establishing the validity of our results. Second, our method allowed the determination of low RBAs (～10~(-4)) of lipophilic ligands, such as dibutyl phthalate. They could not be measured by steady-state IC_(50) assays because of their low solubility. Third, we found that BPA had a surprisingly high k_(on) ＞ 10~4 M~(-1) s~(-1). While its RBA was 1500 times lower than that of 17β estradiol (E2), its k_(on) was ＞1/90 that of E2. As a result, a 10 min surge of BPA from pM to nM could drive the fraction of BPA-activated ERα to a potent 0.1%. This might help to explain the observable estrogenic impacts of BPA.
机译：环境异雌激素破坏内分泌的机制尚不清楚。双酚A（BPA）是一个例子。它在人血清中的浓度低，并且与雌激素受体（ER）的结合较弱。然而，观察到其对前列腺和乳腺发育的影响。我们研究了这种作用是否可以用结合动力学来解释。我们使用荧光偏振各向异性的方法来测量ERα与19种异雌激素结合的动力学速率常数。还从动力学推导了相对结合亲和力（RBA）。我们得出了三个观察结果。首先，我们的RBA与发布的值一致，从而确定了我们结果的有效性。其次，我们的方法允许测定亲脂性配体（如邻苯二甲酸二丁酯）的低RBA（〜10〜（-4））。由于它们的低溶解度，因此无法通过稳态IC_（50）分析进行测量。第三，我们发现BPA的k_（on）＞ 10〜4 M〜（-1）s〜（-1）很高。尽管其RBA比17β雌二醇（E2）低1500倍，但其k_（on）却是E2的1/90。结果，BPA从pM激增至nM 10分钟可将BPA激活的ERα的比例提高到有效的0.1％。这可能有助于解释BPA的可观察到的雌激素作用。

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  • 来源
    《Environmental Science & Technology》 |2014年第19期|11591-11599|共9页
  • 作者

    Kwok-Wing Yiu; Chi-Kin Lee; Ka-Cheung Kwok; Nai-Ho Cheung;

  • 作者单位

    Department of Physics, Hong Kong Baptist University, Kowloon Tong, Hong Kong, People's Republic of China;

    Department of Physics, Hong Kong Baptist University, Kowloon Tong, Hong Kong, People's Republic of China;

    Department of Physics, Hong Kong Baptist University, Kowloon Tong, Hong Kong, People's Republic of China;

    Department of Physics, Hong Kong Baptist University, Kowloon Tong, Hong Kong, People's Republic of 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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