Low-dose signaling toxicity effects of bisphenol compounds on the cooperative action between the nuclear receptors
| Project/Area Number |
19K12340
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 63030:Chemical substance influence on environment-related
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| Research Institution | Sojo University |
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Principal Investigator |
LIU XIAOHUI 崇城大学, 生物生命学部, 准教授 (60596849)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | ビスフェノール / 有害化学物質 / 核内受容体 / シグナル毒性 / 転写制御 / 協働作用 / シグナル毒性効果 |
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| Outline of Research at the Start |
BPAの「低用量効果」は現在でも未解決な「内分泌撹乱物質」問題の核心である。我々は、「その特異的な受容体・エストロゲン関連受容体γ型（ERRγ）である」、「BPAの弱いエストロゲン様活性はERRγを含む一群の自発活性化型核内受容体がERαに協働作用して、活性を大きく増強される」ことを発見した。本研究では、BPAの低用量シグナル毒性効果の核内受容体を介した分子機構解明を目的とし、①自発活性化型核内受容体１３種すべてが協働作用を示す、②ホルモン活性化型核内受容体は一般的に同様の協働作用を受ける、可能性があることを検討する。③一連の 「新世代ビスフェノール」 の活性を調べ、低用量効果を検討する。
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| Outline of Final Research Achievements |
The adverse effects of bisphenol A (BPA) on human health have been believed to occur by “the toxicity in signalling through nuclear receptors (NRs).” To avoid such hazardous BPA, various kinds of BPA-free plasticwares made of so-called next-generation bisphenol compounds are increasingly being seen as important, and are increasingly being produced. However, almost none of these bisphenols have been evaluated for their signalling toxicity. In this study, we attempted to elucidate the molecular mechanisms of such low-dose signalling toxicity of bisphenols. As a result, the following four issues were clarified. (i) ERs are strongly activated by BPA when constitutively self-activated NR co-exists. (ii) There are several bisphenols showing a high risk for human health through some certain NRs. (iii) Some bisphenols act as ERα-agonist and also as ERβ-antagonist. (iv) The structural element responsible for the ERβ-antagonist activity was identified to be the London dispersing force.
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| Academic Significance and Societal Importance of the Research Achievements |
豊かな現代生活を彩る化学製品から漏出する原料ビスフェノールＡ（BPA）。このBPAがもたらす深刻な、メカニズム不明の内分泌撹乱作用。ヒトの健康に悪影響を及ぼすBPAの内分泌撹乱作用は、核内受容体を介したシグナル毒性と考えられている。本研究は、BPAを含む新世代ビスフェノールのこうしたヒト遺伝子に対するシグナル毒性の分子機構を解明しようとするもので、学術的意義、社会的意義はきわめて大きい。また、ヒト核内受容体48種のうち約４分の１存在する自発活性化型核内受容体の、通常の転写因子としての機能とは別な、しかし、本質的に備わった新奇な機能を明らかにする点でもその意義は大きい。
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Report
(4 results)
Research Products
(18 results)
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[Journal Article] Receptor-binding affinities of bisphenol A and its next-generation analogs for human nuclear receptors.2019
Author(s)
X. Liu, H. Sakai, M. Nishigori, K. Suyama, T. Nawaji, S. Ikeda, M. Nishigouchi, H. Okada, A. Matsushima, T. Nose, M. Shimohigashi, Y. Shimohigashi
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Journal Title
Toxicology and applied pharmacology
Volume: 377
Pages: 114610-114610
DOI
Related Report
Peer Reviewed
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