Exploration of molecular mechanism of synergistic effects induced by ER/ERR co-expression which enhances signal toxicity by novel bisphenol derivatives
| Project/Area Number |
17H01881
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Risk sciences of radiation and chemicals
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
野瀬 健 九州大学, 基幹教育院, 教授 (10301334)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2019: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
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| Keywords | 発現制御 / 生体分子 / 生理活性 / 受容体科学 / 分子認識 / 人体有害物質 / 受容体化学 / 蛋白質 |
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| Outline of Final Research Achievements |
Bisphenol A is a raw material of polycarbonate and epoxy resins. This chemical is also known as a harmful environmental chemical, which shows adverse effects even at low doses. The target molecules of environmental chemicals are thought to be nuclear receptors which control gene transcriptions. We have found that the transcriptional activity of an estrogen receptor, which belongs to nuclear receptors, are synergistically increased by co-expression with other nuclear receptors. The aim of this study is to clarify the molecular mechanisms underlying the synergistic effect on transcriptional activity. Finally, we found that several next generation bisphenols bind to the estrogen receptor stronger than bisphenol A.
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| Academic Significance and Societal Importance of the Research Achievements |
現代社会においては、さまざまな化学物質が環境中に放出されている。これらの環境化学物質の安全性の評価は、社会・国民の健康生活にきわめて重要である。現在、有害環境化学物質ビスフェノールAが示す、ごく微量の暴露で悪影響をおよぼす低用量効果は、未解明の課題となっている。本研究では、この解明の端緒として、核内受容体が複数存在することによる活性増強効果の分子機構の解明を目指し、有意義な研究成果を得た。
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Report
(4 results)
Research Products
(48 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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[Journal Article] Phe 2715.39 of Thronbin Receptor PAR-1 is a specific target of Phe-2-phenl group of its tethered ligand2018
Author(s)
Sugiyama, M., Fujita, T., Liu, X., Yutaka, M., Matsushima, A., Shimohigashi, M., and Shimohigashi, Y.
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Journal Title
Peptide Science
Volume: 2017
Pages: 94-95
Related Report
Peer Reviewed
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[Journal Article] Mutual co-work between nuclear receptor ERα and ERRβ requires their homodimerization2018
Author(s)
Liu, X., Shimohigashi, M., Sugiyama, M., Matsushima, A., and Shimohigashi, Y.
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Journal Title
Peptide Science
Volume: 2017,
Pages: 198-199
Related Report
Peer Reviewed
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[Presentation] 新世代ビスフェノールのヒト核内受容体に対する結合活性2019
Author(s)
劉暁輝, 酒井大樹, 錦織充広, 巣山慶太郎, 縄司奨, 池田伸, 西垣内誠, 岡田浩幸, 松島綾美, 野瀬健, 下東美樹, 下東康幸
Organizer
第 92 回日本生化学会大会
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