Estrogen-like effects of low-dose Bisphenol A induced by ERRγ receptor heterodimer

• Project/Area Number: 20710053
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Kyushu University
• Principal Investigator: MATSUSHIMA Ayami Kyushu University, 大学院・理学研究院, 助教 (60404050)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2008: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 内分泌かく乱物質 / 有害化学物質 / 蛋白質 / 分子認識 / 生体分子 / 核内受容体 / 転写因子 / ビスフェノールA / 内分泌撹乱

Research Abstract

This study revealed that the activity of bisphenol A mediated through the estrogen receptor α (ERα) is increased with coexpression of either estrogen-related receptor α (ERRα) or estrogen-related receptor γ (ERRγ). We newly made several series of plasmids to express dimer receptors of ERRα and ERRγ to analyze the activity of ERα. The results indicated that the activity enhancement is due to the interaction between ERα homodimer αnd ERRα homodimer.

Research Products

• [Journal Article] Functional role of the C-terminal Helix 12 peptide in the receptor activation mechanism of estrogen-related receptorγ(ERRγ). (2010)
  • Author(s): Liu, X., Matsushima, A., Okada, H., Shimohigashi, Y
  • Journal Title: Peptide Science 2009 Pages: 435-436
• [Journal Article] Functional role of the C-terminal Helix 12 peptide in the receptor activation mechanism of estrogen-related receptorγ(ERRγ). (2010)
  • Author(s): Liu, X., Matsushima, A., Okada, H., Shimohigashi, Y.
  • Journal Title: Peptide Science 2009 Pages: 435-436
• [Journal Article] Functional role of the C-terminal Helix 12 peptide in the receptor activation mechanism of estrogen-related receptor γ (ERRγ). (2010)
  • Author(s): Liu, X., Matsushima, A., Okada, H., Shimohigashi, Y.
  • Journal Title: Peptide Science 2009 Pages: 435-436
  • Peer Reviewed
• [Journal Article] Discriminatory synergistic effect of Trp-substitutions in supERαgonist [(Arg/Lys)14, (Arg/Lys)15]nociceptin on ORL1 receptor binding and activation. (2009)
  • Author(s): Nishimura, H., Li, J., Isozaki, K., Okada, K., Matsushima, A., Nose, T., Costa, T., Shimohigashi, Y.
  • Journal Title: Bioorg. Med. Chem. 17 Pages: 5683-5687
• [Journal Article] Placenta expressing the greatest quantity of bisphenol A receptor ERRγamong the human reproductive tissues: predominant expression of type-1 ERRγisoform. (2009)
  • Author(s): Takeda, Y., Liu, X., Sumiyoshi, M., Matsushima, A., Shimohigashi, M., Shimohigashi, Y.
  • Journal Title: J. Biochem. 146 Pages: 113-122
  • NAID: 10025187684
• [Journal Article] Spare intERαctions of highly potent [Arg14, Lys15]nociceptin for cooperative induction of ORL1 receptor activation. (2009)
  • Author(s): Isozaki, K., Li, J., Okada, K., Nishimura H., Matsushima, A., Nose, T., Costa, T., Shimohigashi, Y.
  • Journal Title: Bioorg. Med. Chem. 17 Pages: 7904-7908
• [Journal Article] ERα/ERRαNuclear Receptor Heterodimer Directly Linked by A Flag Peptide. (2009)
  • Author(s): Ikeda, S., Matsushim, A., Shimohigashi, Y
  • Journal Title: Peptide Science 2008 Pages: 511-512
• [Journal Article] Discriminatory synergistic effect of Trp-substitutions in superagonist [(Arg/Lys)^<14>, (Arg/Lys)^<15>] nociceptin on ORL1 receptor binding and activation. (2009)
  • Author(s): Nishimura, H., Li, J., Isozaki, K., Okada, K., Matsushima, A., Nose, T., Costa, T., Shimohigashi, Y.
  • Journal Title: Bioorg. Med. Chem. 17 Pages: 5683-5687
  • Peer Reviewed
• [Journal Article] Placenta expressing the greatest quantity of bisphenol A receptor ERRγ among the human reproductive tissues: predominant expression of type-1 ERRγ isoform. (2009)
  • Author(s): Takeda, Y., Liu, X., Sumiyoshi, M., Matsushima, A., Shimohigashi, M., Shimohigashi, Y.
  • Journal Title: J. Biochem. 146 Pages: 113-122
  • NAID: 10025187684
  • Peer Reviewed
• [Journal Article] Spare interactions of highly potent [Arg14, Lys15] nociceptin for cooperative induction of ORL1 receptor activation. (2009)
  • Author(s): Isozaki, K., Li, J., Okada, K., Nishi mura H., Matsushima, A., Nose, T., Costa, T., Shimohigashi, Y.
  • Journal Title: Bioorg. Med. Chem. 17 Pages: 7904-7908
  • Peer Reviewed
• [Journal Article] Induced-fit type ligand binding guided by free-rotatory Leu residue present in the 7th a-helix peptide in the estrogen-related receptor γ (ERRγ) (2009)
  • Author(s): Matsushima, A., Okada, H., Liu, X., Tokunaga, T., Teramoto, T., Kakuta. Y. Shimohigashi, Y.
  • Journal Title: Peptide Science 2008 Pages: 521-522
  • Peer Reviewed
• [Journal Article] ERa/ERRa Nuclear Receptor Heterodimer Directly Linked by A Flag Peptide (2009)
  • Author(s): Ikeda, S., Matsushim, A., and Shimohigashi, Y.
  • Journal Title: Peptide Science 2008 Pages: 511-512
  • Peer Reviewed
• [Journal Article] Bisphenol A-specific nuclear receptor ERRy : structure-function analysis of the two novel isoforms lacking vital peptide fragment in the ligand binding domain (2009)
  • Author(s): Takeda, Y., Liu, X., Sumiyoshi, M., Matsushima, A., Shimohigashi, Y. and Shimohigashi, M.
  • Journal Title: Peptide Science 2008 Pages: 517-518
  • Peer Reviewed
• [Journal Article] Induced-fit type ligand binding guided by free-rotatory Leu residue present in the 7thα-helix peptide in the estrogen-related receptorγ(ERRγ). (2008)
  • Author(s): Matsushima, A., Okada, H., Liu, X., Tokunaga, T., TERαmoto, T., Kakuta, Y., Shimohigashi, Y.
  • Journal Title: Peptide Science 2008 Pages: 521-522
  • NAID: 10027166812
• [Journal Article] Bisphenol A-specific nuclear receptor ERRγ: structure-function analysis of the two novel isoforms lacking vital peptide fragment in the ligand binding domain. (2008)
  • Author(s): Takeda, Y., Liu, X., Sumiyoshi, M., Matsushima, A., Shimohigashi, Y., Shimohigashi, M.
  • Journal Title: Peptide Science 2008 Pages: 517-518
  • NAID: 10027166800
• [Journal Article] Direct evidence revealing structural elements essential for the high binding ability of bisphenol A to human estrogen-related receptorγ(ERRγ). (2008)
  • Author(s): Okada, H., Tokunaga, T., Lui, X., Takayanagi, S., Matsushima, A., Shimohigashi, Y.
  • Journal Title: Environ. Health Perspect. 116 Pages: 32-38
• [Journal Article] ERRγtethers strongly bisphenol A and 4-α-cumylphenol in an induced-fit manner. (2008)
  • Author(s): Matsushima. A., Teramoto, T., Okada, H., Liu, X., Tokunaga, T., Kakuta, Y., Shimohigashi, Y.
  • Journal Title: Biochem. Biophys. Res. Commun. 373 Pages: 408-413
• [Journal Article] A strategy to explore the target receptor of endocrine disruptors: Estrogen-relatedreceptorγ(ERRγ) as a genuine acceptor of (2008)
  • Author(s): Matsushima, A., Shimohigashi, Y.
  • Journal Title: Alternatives to Animal Testing and Experimentation. (AATEX journal) special issue Pages: 495-497
• [Journal Article] Radar chart deviation analysis of prion protein amino acid composition defines characteristic structural abnormalities of the N-terminal octapeptide tandem repeat. (2008)
  • Author(s): Yokotani, S., Nose, T., Horiuchi, Y., Matsushima, A., Shimohigashi, Y.
  • Journal Title: Protein Peptide Sci. 15 Pages: 949-955
• [Journal Article] Design synthesis of highly potent antagonist of ORL1 nociceptin receptor. (2008)
  • Author(s): Li, J. Isozaki, K., Okada, K., Matsushima, A., Nose, T., Costa, T., Shimohigashi, Y.
  • Journal Title: Bioorg. Med. Chem. 16 Pages: 2635-3664
• [Journal Article] Direct evidence revealing structural elements essential for the high binding ability of bisphenol A to human estrogen-related receptor γ (ERRγ) (2008)
  • Author(s): Okada, H., Tokunaga, T., Lui, X., T akayanagi, S., Matsushima, A., and Shimohigashi, Y.
  • Journal Title: Environ. Health Perspect 116 Pages: 32-38
  • Peer Reviewed
• [Journal Article] ERRy tethers strongly bisphenol A and 4-a-cumylphenol in an induced-fit manner (2008)
  • Author(s): Matsushima. A., Teramoto, T., Okad a, H., Liu, X., Tokunaga, T., Kakut a, Y., and Shimohigashi, Y.
  • Journal Title: Biochem. Biophys. Res. Commun 373 Pages: 373-373
  • Peer Reviewed
• [Journal Article] A strategy to explore the target receptor of endocrine disruptors : Estrogen-related receptor γ (ERR γ) as a genuine acceptor of bisphenol A (2008)
  • Author(s): Matsushima, A., Shimohigashi, Y.
  • Journal Title: Alternatives to Animal Testing and Experimentation. (AATEXjournal) special issue Pages: 495-497
• [Journal Article] Radar chart deviation analysis of prion protein amino acid composition defines characteristic structural abnormalities of the N-terminal octapeptide tandem repeat (2008)
  • Author(s): Yokotani, S., Nose, T., Horiuchi, Y., Matsushima, A., and Shimohigashi, Y.
  • Journal Title: Protein Peptide Sci 15 Pages: 949-955
  • Peer Reviewed
• [Journal Article] Design synthesis of highly potent antagonist of ORL1 nociceptin receptor (2008)
  • Author(s): Li, I Isozaki, K., Okada, K., Matsu shima, A., Nose, T., Costa, T., and Shimohigashi, Y.
  • Journal Title: Bioorg. Med. Chem 16 Pages: 2635-2664
  • Peer Reviewed
• [Journal Article] Bisphenol AF is a Full Agonist for the Estrogen Receptor ERα, but a Highly Specific Antagonist for ERβ.
  • Author(s): Matsushima, A., Liu, X., Okada, H., Shimohigashi, M., Shimohigashi, Y.
  • Journal Title: Environ. Health Perspect. (in press)
• [Journal Article] Distinction of the binding modes for human nuclear receptor ERRγbetween bisphenol A and 4-hydroxytamoxifen.
  • Author(s): Liu, X., Matsushima, A., Okada, H., Shimohigashi, Y.
  • Journal Title: J. Biochem (in press)
  • NAID: 10027877932
• [Journal Article] Bisphenol AF is a Full Agonist for the Estrogen Receptor ERα, but a Highly Specific Antagonist for ERβ.
  • Author(s): Matsushima, A., Liu, X., Okada, H., Shimohigashi, M., Shimohigashi, Y.
  • Journal Title: Environ. Health Perspect. (in press)
  • Peer Reviewed
• [Journal Article] Distinction of the binding modes for human nuclear receptor ERRγ between bisphenol A and 4-hydroxytamoxifen.
  • Author(s): Liu, X., Matsushima, A., Okada, H., Shimohigashi, Y.
  • Journal Title: J. Biochem. (in press)
  • NAID: 10027877932
  • Peer Reviewed
• [Presentation] マウス胎仔期における自発活性化型核内受容体の発現解析 (2009)
  • Author(s): 赤岩裕也、松島綾美、武田行正、下東康幸
  • Organizer: 第46回化学関連支部合同九州大会
  • Place of Presentation: 北九州国際会議場(北九州市)
  • Year and Date: 2009-07-11
• [Presentation] マウス胎仔期における自発活性化型核内受容体の発現解析 (2009)
  • Author(s): 赤岩裕也、松島綾美、武田行正、下東康幸
  • Organizer: 第46回化学関連支部合同九州大会
  • Place of Presentation: 北九州国際会議場、北九州市
  • Year and Date: 2009-07-11
• [Presentation] エストロゲン関連受容体γ(ERRγ)誘導体のリガンド結合選択性および自発活性化要因の解析 (2009)
  • Author(s): 劉暁輝、松島綾美、岡田浩幸、下東康幸
  • Organizer: 平成21年度日本生化学会九州支部例会
  • Place of Presentation: 九州大学(福岡市
• [Presentation] エストロゲン受容体α型(ERα)とエストロゲン関連受容体α型(ERRα)の転写活性制御機構の解析 (2009)
  • Author(s): 池田伸、松島綾美、下東康幸
  • Place of Presentation: 九州大学(福岡市)
• [Presentation] Synergistic transactivation of estrogen receptorαand estrogen-related receptorα (2009)
  • Author(s): 池田伸、松島綾美、下東康幸
  • Organizer: 第19回日韓ジョイントセミナー
  • Place of Presentation: 釜山(韓国)
• [Presentation] ERαおよびERRα共発現による相乗的活性増強作用の解析 (2009)
  • Author(s): 池田伸、松島綾美、下東康幸
  • Organizer: 第82回日本生化学会大会
• [Presentation] 受容体活性化機構におけるエストロゲン関連受容体γ型(ERRγ)C端ヘリクッス12ペプチドの寄与 (2009)
  • Author(s): 劉曉輝、松島綾美、岡田浩幸、下東康幸
  • Organizer: 第46回ペプチド討論会
  • Place of Presentation: 神戸ポートアイランド(神戸)
• [Presentation] ERαおよびERRファミリーの共発現細胞でのエストロゲンの効果 (2009)
  • Author(s): 池田伸、松島綾美、下東康幸
  • Organizer: 環境ホルモン学会第12回研究発表会
  • Place of Presentation: 東京大学山上会館(東京)
• [Presentation] ERαおよびERRファミリーの共発現細胞でのエストロゲンの効果 (2009)
  • Author(s): 池田伸、松島綾美、下東康幸
  • Organizer: 環境ホルモン学会第12回研究発表会
  • Place of Presentation: 星陵会館および東京ビッグサイト(江東区)
• [Presentation] エストロゲン関連受容体γ(ERRγ)誘導体のリガンド結合選択性および自発活性化要因の解析 (2009)
  • Author(s): 劉暁輝、松島綾美、岡田浩幸、下東康幸
  • Organizer: 平成21年度日本生化学会九州支部例会
  • Place of Presentation: 九州大学、福岡市
• [Presentation] エストロゲン受容体α型(ERα)とエストロゲン関連受容体α型(ERRα)の転写活性制御機構の解析 (2009)
  • Author(s): 池田伸、松島綾美、下東康幸
  • Organizer: 平成21年度日本生化学会九州支部例会
  • Place of Presentation: 九州大学、福岡市
• [Presentation] Synergistic transactivation of estrogen receptor α and estrogen-related receptor α (2009)
  • Author(s): 池田伸、松島綾美、下東康幸
  • Organizer: 第19回日韓ジョイントセミナー
  • Place of Presentation: 釜山展示場、釜山、韓国
• [Presentation] 受容体活性化機構におけるエストロゲン関連受容体γ型(ERRγ)C端ヘリクッス12ペプチドの寄与 (2009)
  • Author(s): 劉曉輝、松島綾美、岡田浩幸、下東康幸
  • Organizer: 第46回ペプチド討論会
  • Place of Presentation: 北九州国際会議場、北九州市
• [Presentation] ERαおよびERRファミリーの共発現細胞でのエストロゲンの効果 (2009)
  • Author(s): 池田伸、松島綾美、下東康幸
  • Organizer: 環境ホルモン学会第12回研究発表会
  • Place of Presentation: 東京大学山上会館、東京
• [Presentation] エストロゲン受容体α型とエストロゲン関連受容体α型とのへテロダイマーの新規発現系構築とその活性評価 (2008)
  • Author(s): 池田伸、松島綾美、下東康幸
  • Organizer: 第45回化学関連支部会
  • Place of Presentation: 北九州国際会議場(北九州市)
  • Year and Date: 2008-07-05
• [Presentation] エストロゲン受容体α型とエストロゲン関連受容体α型とのヘテロダイマーの新規発現系構築とその活性評価 (2008)
  • Author(s): 池田伸、松島綾美、下東康幸
  • Organizer: 第45回化学関連支部会
  • Place of Presentation: 北九州国際会議場、北九州市
  • Year and Date: 2008-07-05
• [Presentation] ビスフェノールA類似化合物のERRγ結合要因解析 (2008)
  • Author(s): 松島綾美、寺本岳大、岡田浩幸、劉暁 輝、角田佳充、木村誠、下東康幸
  • Organizer: 平成20年度日本生化学会九州支部例会
  • Place of Presentation: 九州大学(福岡市)
• [Presentation] ビスフェノールA結合におけるエストロゲン関連受容体γ型(ERRγ)の構造要因解析 (2008)
  • Author(s): 劉暁輝、松島綾美、徳永隆俊、岡田浩幸、下東康幸
  • Organizer: 平成20年度日本生化学会九州支部例会
  • Place of Presentation: 九州大学(福岡市)
• [Presentation] エストロゲン関連受容体γ型と内分泌撹乱物質ビスフェノールAおよびその誘導体4-α-クミルフェノールの誘導適合による結合様式 (2008)
  • Author(s): Ayami Matsushima, Hiroyuki Okada, Xiaohui Liu, Takatoshi Tokunaga, Takamasa Teramoto, Yoshimitsu Kakuta, Yasuyuki Shimohigashi
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会(BMB2008)
  • Place of Presentation: 神戸ポートアイランド(神戸)
• [Presentation] エストロゲン関連受容体γ型第ヘリックスペプチドのLeu側鎖の自由回転による適合誘導型リガンド結合 (2008)
  • Author(s): 松島綾美、岡田浩幸、劉暁輝、徳永隆俊、寺本岳大、角田佳充、下東康幸
  • Organizer: 第45回ペプチド討論会
  • Place of Presentation: タワーホール船堀(江戸川区)
• [Presentation] (2008)
  • Author(s): 松島綾美、岡田浩幸、寺本岳大、劉暁 輝、角田佳充、下東康幸
  • Organizer: 環境ホルモン学会第11回研究発表会
  • Place of Presentation: 星陵会館および東京ビッグサイト(江東区)
• [Presentation] ビスフェノールA類似化合物のERRγ結合要因解析 (2008)
  • Author(s): 松島綾美、寺本岳大、岡田浩幸、劉暁輝、角田佳充、木村誠、下東康幸
  • Organizer: 平成20年度日本生化学会九州支部例会
  • Place of Presentation: 九州大学、福岡市
• [Presentation] ビスフェノールA結合におけるエストロゲン関連受容体γ型(ERRγ)の構造要因解析 (2008)
  • Author(s): 劉暁輝、松島綾美、徳永隆俊、岡田浩幸、下東康幸
  • Organizer: 平成20年度日本生化学会九州支部例会
  • Place of Presentation: 九州大学、福岡市
• [Presentation] Structural flexibility of human nuclear receptor ERR to adopt endocrine disruptor bisphenol A and its derivatives (2008)
  • Author(s): Ayami Matsushima, Hiroyuki Okada, Xiaohui Liu, Takatoshi Tokunaga, T akamasa Teramoto Yoshimitsu Kaku ta, and Yasuvuki Shimohigashi
  • Organizer: 17th Meeting of Methods in Protein Structure Analysis(MPSA2008)
  • Place of Presentation: 北海道大学、札幌市
• [Presentation] エストロゲン関連受容体γ型と内分泌撹乱物質ビスフェノールAおよびその誘導体4-α-クミルフェノールの誘導適合による結合様式 (2008)
  • Author(s): 松島綾美、岡田浩幸、寺本岳大、劉暁輝、角田佳充、下東康幸
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会(BMB2008)
  • Place of Presentation: 神戸ポートアイランド、神戸市
• [Presentation] エストロゲン関連受容体γ型第ヘリックスペプチドのLeu側鎖の自由回転による適合誘導型リガンド結合 (2008)
  • Author(s): 松島綾美、岡田浩幸、劉暁輝、徳永隆俊、寺本岳大、角田佳充、下東康幸
  • Organizer: 第45回ペプチド討論会
  • Place of Presentation: タワーホール船堀、東京都江戸川区
• [Presentation] ビスフェノールAおよびその類似体とエストロゲン関連受容体γ型(ERRγ)とのX線結晶構造解析による結合要因解析 (2008)
  • Author(s): 松島綾美、岡田浩幸、寺本岳大、劉暁輝、角田佳充、下東康幸
  • Organizer: 環境ホルモン学会第11回研究発表会
  • Place of Presentation: 星陵会館および東京ビッグサイト、東京都江東区
• [Remarks]
  • URL: http://lsfb.scc.kyushu-u.ac.jp/