Receptor-binding affinities of bisphenol A and its next-generation analogs for human nuclear receptors

Xiaohui Liu, Hiroki Sakai, Mitsuhiro Nishigori, Keitaro Suyama, Tasuku Nawaji, Shin Ikeda, Makoto Nishigouchi, Hiroyuki Okada, Ayami Matsushima, Takeru Nose, Miki Shimohigashi, Yasuyuki Shimohigashi

研究成果: ジャーナルへの寄稿記事

抄録

An endocrine-disrupting chemical Bisphenol A (BPA) binds specifically to a nuclear receptor (NR) named ERRγ. Although the importance of receptor-binding evaluation for human NRs is often stressed, the binding characteristics of so-called next-generation (NextGen) bisphenol compounds are still poorly understood. The ultimate objective of this investigation was to evaluate BPA and its NextGen analogs for their abilities to bind to 21 human NRs, the greatest members of NRs for which tritium-labeled specific ligands were available. After establishing the detailed assay conditions for each NR, the receptor binding affinities of total 11 bisphenols were evaluated in competitive binding assays. The results clearly revealed that BPA and the NextGen bisphenols of BPAF, BPAP, BPB, BPC, BPE, and BPZ were highly potent against one or more of NRs such as CAR, ERα, ERβ, ERRγ, and GR, with IC50 values of 3.3–73 nM. These bisphenols were suggested strongly to be disruptive to these NRs. BPM and BPP also appeared to be disruptive, but less potently. BPF exhibited only weak effects and only against estrogen-related NRs. Surprisingly, most doubtful bisphenol BPS was supposed not to be disruptive. The NRs to which BPA and NextGen bisphenols did not bind were RARα, RARβ, RARγ, and VDR. PPARγ, RORα, RORβ, RORγ, RXRα, RXRβ, and RXRγ, exhibited very weak interaction with these bisphenols. The ten remaining NRs, namely, ERRγ, ERβ, ERα, CAR, GR, PXR, PR, AR, LXRβ, and LXRα, showed distinctly strong binding to some bisphenols in this order, being likely to have consequential endocrine-disruption effects.

元の言語英語
記事番号114610
ジャーナルToxicology and Applied Pharmacology
377
DOI
出版物ステータス出版済み - 8 15 2019

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Cytoplasmic and Nuclear Receptors
Assays
Endocrine Disruptors
Peroxisome Proliferator-Activated Receptors
Competitive Binding
Tritium
Inhibitory Concentration 50
Estrogens
Railroad cars
Ligands
bisphenol A

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Pharmacology

これを引用

Receptor-binding affinities of bisphenol A and its next-generation analogs for human nuclear receptors. / Liu, Xiaohui; Sakai, Hiroki; Nishigori, Mitsuhiro; Suyama, Keitaro; Nawaji, Tasuku; Ikeda, Shin; Nishigouchi, Makoto; Okada, Hiroyuki; Matsushima, Ayami; Nose, Takeru; Shimohigashi, Miki; Shimohigashi, Yasuyuki.

:: Toxicology and Applied Pharmacology, 巻 377, 114610, 15.08.2019.

研究成果: ジャーナルへの寄稿記事

Liu, X, Sakai, H, Nishigori, M, Suyama, K, Nawaji, T, Ikeda, S, Nishigouchi, M, Okada, H, Matsushima, A, Nose, T, Shimohigashi, M & Shimohigashi, Y 2019, 'Receptor-binding affinities of bisphenol A and its next-generation analogs for human nuclear receptors', Toxicology and Applied Pharmacology, 巻. 377, 114610. https://doi.org/10.1016/j.taap.2019.114610
Liu, Xiaohui ; Sakai, Hiroki ; Nishigori, Mitsuhiro ; Suyama, Keitaro ; Nawaji, Tasuku ; Ikeda, Shin ; Nishigouchi, Makoto ; Okada, Hiroyuki ; Matsushima, Ayami ; Nose, Takeru ; Shimohigashi, Miki ; Shimohigashi, Yasuyuki. / Receptor-binding affinities of bisphenol A and its next-generation analogs for human nuclear receptors. :: Toxicology and Applied Pharmacology. 2019 ; 巻 377.
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abstract = "An endocrine-disrupting chemical Bisphenol A (BPA) binds specifically to a nuclear receptor (NR) named ERRγ. Although the importance of receptor-binding evaluation for human NRs is often stressed, the binding characteristics of so-called next-generation (NextGen) bisphenol compounds are still poorly understood. The ultimate objective of this investigation was to evaluate BPA and its NextGen analogs for their abilities to bind to 21 human NRs, the greatest members of NRs for which tritium-labeled specific ligands were available. After establishing the detailed assay conditions for each NR, the receptor binding affinities of total 11 bisphenols were evaluated in competitive binding assays. The results clearly revealed that BPA and the NextGen bisphenols of BPAF, BPAP, BPB, BPC, BPE, and BPZ were highly potent against one or more of NRs such as CAR, ERα, ERβ, ERRγ, and GR, with IC50 values of 3.3–73 nM. These bisphenols were suggested strongly to be disruptive to these NRs. BPM and BPP also appeared to be disruptive, but less potently. BPF exhibited only weak effects and only against estrogen-related NRs. Surprisingly, most doubtful bisphenol BPS was supposed not to be disruptive. The NRs to which BPA and NextGen bisphenols did not bind were RARα, RARβ, RARγ, and VDR. PPARγ, RORα, RORβ, RORγ, RXRα, RXRβ, and RXRγ, exhibited very weak interaction with these bisphenols. The ten remaining NRs, namely, ERRγ, ERβ, ERα, CAR, GR, PXR, PR, AR, LXRβ, and LXRα, showed distinctly strong binding to some bisphenols in this order, being likely to have consequential endocrine-disruption effects.",
author = "Xiaohui Liu and Hiroki Sakai and Mitsuhiro Nishigori and Keitaro Suyama and Tasuku Nawaji and Shin Ikeda and Makoto Nishigouchi and Hiroyuki Okada and Ayami Matsushima and Takeru Nose and Miki Shimohigashi and Yasuyuki Shimohigashi",
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T1 - Receptor-binding affinities of bisphenol A and its next-generation analogs for human nuclear receptors

AU - Liu, Xiaohui

AU - Sakai, Hiroki

AU - Nishigori, Mitsuhiro

AU - Suyama, Keitaro

AU - Nawaji, Tasuku

AU - Ikeda, Shin

AU - Nishigouchi, Makoto

AU - Okada, Hiroyuki

AU - Matsushima, Ayami

AU - Nose, Takeru

AU - Shimohigashi, Miki

AU - Shimohigashi, Yasuyuki

PY - 2019/8/15

Y1 - 2019/8/15

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