Elucidation of bisphenol A low-dose effects mediated through the nuclear receptor ERRγ

2009 Fiscal Year Final Research Report

• Project/Area Number: 19201012
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Kyushu University
• Principal Investigator: SHIMOHIGASHI Yasuyuki Kyushu University, 大学院・理学研究院, 教授 (00211293)
• Co-Investigator(Kenkyū-buntansha): KAKUTA Yoshimitsu 九州大学, 大学院・農学研究院, 准教授 (00314360) ; SHIMOHIGASHI Miki 福岡大学, 理学部, 講師 (60078590) ; NOSE Takeru 九州大学, 大学院・理学研究院, 准教授 (10301334) ; MATSUSHIMA Ayami 九州大学, 大学院・理学研究院, 助教 (60404050)
• Project Period (FY): 2007 – 2009
• Keywords: 内分泌かく乱物質 / 有害化学物質 / 核内受容体 / 低用量効果 / ビスフェノール

Research Abstract

The issue of low-dose effects of endocrine disruptor bisphenol A (BPA) is currently immense social difficulty unsolved. In the present study, we clarified several transcription factors regulated by BPA's target estrogen-related receptor gamma (ERRγ), and found that BPA inhibits the Neuro2a's neuron projection mediated through ERRγ. We also elucidated that BPA administration on the fruit fly Drosophila afford the adverse effects on their circadian rhythms by eliciting a hyperactivity disorder.

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., Y. Shimohigashi
  • Journal Title: Peptide Science 2009 Pages: 435-436
  • Peer Reviewed
• [Journal Article] Discriminatory Synergistic Effect of Trp-substitutions in Superagonist [(Arg, Lys)14-15]nociceptins on ORL1 Receptor Binding and Activation. (2009)
  • Author(s): H. Nishimura, J. Li, K. Isozaki, K. Okada, A. Matsushima, T. Nose, T. Costa, Y. Shimohigashi
  • Journal Title: Bioorganic & Medicinal Chemistry 17(15) Pages: 5683-5687
  • Peer Reviewed
• [Journal Article] 放射標識化合物を用いた受容体結合試験による特異的受容体の同定・解析:ビスフェノールaが結合する特異的受容体ERRγ (2009)
  • Author(s): 岡田浩幸, 下東康幸
  • Journal Title: RADIOISOTOPES 58 Pages: 43-46
  • Peer Reviewed
• [Journal Article] Exploration of endocrine disrupting chemicals on estrogen receptorαby the agonist/antagonist differential-docking screening method (2009)
  • Author(s): T. Nose, T. Tokunaga, Y. Shimohigashi
  • Journal Title: Toxicology Letter 191(1) Pages: 33-39
  • Peer Reviewed
• [Journal Article] ERα/ERRαnuclear receptor heterodimer directly linked by a flag peptide. (2009)
  • Author(s): S. Ikeda, A. Matsushima, Y. Shimohigashi
  • Journal Title: Peptide Science 2008 Pages: 511-512
  • Peer Reviewed
• [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): Y. Takeda, X. Liu, M. Sumiyoshi, A. Matsushima, M. Shimohigashi, Y. Shimohigashi
  • Journal Title: Journal of Biochemistry 146 Pages: 113-122
  • Peer Reviewed
• [Journal Article] ERRγtethers strongly bisphenol A and 4-α-cumylphenol in an induced-fit manner. (2008)
  • Author(s): A. Matsushima, T. Teramoto, H. Okada, X. Liu, T. Tokunaga, Y. Kakuta, Y. Shimohigashi
  • Journal Title: Biochem. Biophys. Res. Commun 373 Pages: 408-413
  • Peer Reviewed
• [Journal Article] A strategy to explore the target receptor of endocrine disruptors: Estrogen-related receptorγ(ERRγ) as a genuine acceptor of bisphenol A. (2008)
  • Author(s): A. Matsushima, Y. Shimohigashi
  • Journal Title: Alternatives to Animal Testing and Experimentation. (AATEX journal) special issue Pages: 495-497
  • Peer Reviewed
• [Journal Article] Relationship between the Results of in vitro Receptor Binding Assay to Human Estrogen Receptorαand in vivo Uterotrophic Assay: Comparative Study with 65 Selected Chemicals (2008)
  • Author(s): Y. Akahori, M. Nakai, K. Yamasaki, M. Takatsuki, Y. Shimohigashi, M. Ohtaki
  • Journal Title: Toxicology in Vitro 22 Pages: 225-23
  • Peer Reviewed
• [Journal Article] Direct Measure of Fluorescence Intensity for Efficient Receptor-binding Assay: Conjugates of Ethinylcarboxyestradiol and 5(and 6)-Carboxyfluorescein viaα, ω-Diaminoalkanes as a Tracer for Estrogen Receptor (2008)
  • Author(s): D. Asai, T. Tokunaga, K. Kondo, T. Kawaguchi, S. Takayanagi, T. Shinmyozu, M. Nakai, Y. Yakabe, Y. Shimohigashi
  • Journal Title: Journal of Biochemistry 143 Pages: 781-792
  • Peer Reviewed
• [Journal Article] A Docking modeling rationally predicts strong binding of bisphenol A to estrogen-related receptorγ (2008)
  • Author(s): T. Nose, Y. Shimohigashi
  • Journal Title: Protein & Peptide Letters 15 Pages: 290-296
  • Peer Reviewed
• [Journal Article] Direct Evidence Revealing Structural Elements Essential for the High Binding Ability of Bisphenol A to Human Estrogen-related Receptor-γ (2008)
  • Author(s): H. Okada, T. Tokunaga, X. Liu, S. Takayanagi, A. Matsushima, Y. Shimohigashi
  • Journal Title: Environmental Health Perspectives 116 Pages: 32-38
  • Peer Reviewed
• [Journal Article] Receptor binding characteristics of endocrine disruptor bisphenol A. Chief and Corroborative Hydrogen Bonds of Bisphenol A Phenol-hydroxyl Group with Arg316 and Glu275 Residues in the Human Nuclear Receptor of Estrogen-related Receptorγ(ERRγ) (2007)
  • Author(s): X. Liu, A. Matsushima, H. Okada, T. Tokunaga, K. Isozaki, Y. Shimohigashi
  • Journal Title: FEBS Journal 274 Pages: 6340-6351
  • Peer Reviewed
• [Journal Article] Structural Evidence for Endocrine Disruptor Bisphenol A Binding to Human Nuclear Receptor ERRγ (2007)
  • Author(s): A. Matsushima, Y. Kakuta, T. Teramoto, Koshiba, T., X. Liu, H. Okada, T. Tokunaga, S. Kawabata, M. Kimura, Y. Shimohigashi
  • Journal Title: Journal of Biochemistry 142(4) Pages: 517-524
  • Peer Reviewed
• [Journal Article] Distinction of the binding modes for human nuclear receptor ERRγbetween bisphenol A and 4-hydroxytamoxifen.
  • Author(s): Liu, X., A. Matsushima, Okada, H., Y.
  • Journal Title: J. Biochem (in press)
  • 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., Y. Shimohigashi
  • Journal Title: Environ. Health Perspect (in press)
  • Peer Reviewed
• [Presentation] ビスフェノールAFはERαには強いアゴニスト、ERβには強いアンタゴニストである (2009)
  • Author(s): 下東康幸, 劉暁輝, 岡田浩幸, 松島綾美, 下東美樹
  • Organizer: 環境ホルモン学会第12回研究発表会
  • Place of Presentation: 東京
  • Year and Date: 20091207-20091208
• [Presentation] ヒト核内受容体ERRγ・C端へリックス12のリガンド結合性および受容体活性化機構 (2009)
  • Author(s): 劉暁輝, 松島綾美, 岡田浩幸, 下東美樹, 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
  • Year and Date: 20091207-20091208
• [Presentation] 核内受容体CARにおけるビスフェノール化合物の応答性解析 (2009)
  • Author(s): 酒井大樹, 劉暁輝, 岡田浩幸, 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
  • Year and Date: 20091207-20091208
• [Presentation] 500化学物資のレチノイド関連オーファン受容体β型(RORβ)への結合性 (2009)
  • Author(s): 錦織充広, 野瀬健, 下東康幸
  • Organizer: 環境ホルモン学会第12回研究発表会
  • Year and Date: 20091207-20091208
• [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
  • Year and Date: 20091207-20091208
• [Presentation] 核内受容体Rev-ervsに対するヘム結合性の分光学的測定 (2009)
  • Author(s): 永田祐介, 野瀬健, 錦織充広, 下東康幸
  • Organizer: 環境ホルモン学会第12回研究発表会
  • Year and Date: 20091207-20091208
• [Presentation] 核内受容体PPARγにおける500物質のスクリーニング (2009)
  • Author(s): 下東美樹, 山田隆弘, 久間祥子, 住吉美保, 古賀啓太, 松島綾美, 中川裕之, 下東康幸
  • Organizer: 環境ホルモン学会第12回研究発表会
  • Year and Date: 20091207-20091208
• [Presentation] 核内受容体PPARγにおける500物質のスクリーニング (2009)
  • Author(s): 酒井大樹, 劉暁輝, 岡田浩幸, 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
  • Year and Date: 20091207-20091208
• [Presentation] 内分泌撹乱化学物質・ビスフェノールaのショウジョウバエ核内受容体に及ぼす影響. (2009)
  • Author(s): 下東美樹, 松永裕美, 住吉美保, 岡田浩幸, 古賀啓太, 松島綾美, 下東康幸
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 20091021-20091024
• [Presentation] マウス胎仔期に発現ピークを示す核内受容体遺伝子の解析. (2009)
  • Author(s): 赤岩裕也, 松島綾美, 武田行正, 下東康幸
  • Organizer: 第82回日本生化学会大会
  • Year and Date: 20091021-20091024
• [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
  • Year and Date: 20081213-20081214
• [Presentation] 環境ホルモン・ビスフェノールa暴露によるショウジョウバエの行動リズム変異 (2008)
  • Author(s): 下東美樹, 府本優, 伊藤太一, 劉暁輝, 松島綾美, 谷村禎一, Ian A. Meinertzhagen, 中川裕之, 松本顕, 下東康幸
  • Organizer: 環境ホルモン学会第11回研究発表会
  • Year and Date: 20081213-20081214
• [Presentation] エストロゲン受容体α型に選択的に結合する環境ホルモン・ビスフェノールaf (2008)
  • Author(s): 岡田浩幸, 劉暁輝, 松島綾美, 下東康幸
  • Organizer: 環境ホルモン学会第11回研究発表会
  • Year and Date: 20081213-20081214
• [Presentation] ビスフェノールaのエストロゲン関連受容体γ型への強い結合を支える受容体Leu345およびVal313残基 (2008)
  • Author(s): 劉暁輝, 松島綾美, 徳永隆俊, 岡田浩幸, 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
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 20081209-20081212
• [Presentation] 胎盤・胎児脳に高発現の自発活性化型核内受容体ERRγに対する環境ホルモン・ビスフェノールaの結合とリスク (2008)
  • Author(s): 下東康幸
  • Organizer: 第101回日本繁殖生物学会
  • Place of Presentation: 福岡
  • Year and Date: 2008-09-19
• [Presentation] ビスフェノールA受容体ERRγとそのアイソフォームのヒト脳および生殖器官における発現分布 (2007)
  • Author(s): 武田行正, 劉暁輝, 松島綾美, 下東美樹, 下東康幸
  • Organizer: 第30回日本分子生物学会年会、第80回日本生化学会大会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 20071211-20071215
• [Presentation] 結晶構造から明らかになったビスフェノールa受容体の結合構造要因 (2007)
  • Author(s): 下東美樹, 堤俊博, 劉暁輝, 徳永隆俊, Ian A. Meinertzhagen, 下東康幸
  • Organizer: 第10回環境ホルモン学会研究発表会
  • Place of Presentation: 大宮
  • Year and Date: 20071210-20071211
• [Presentation] ビスフェノールaはステロイドホルモン核内受容体9種うちERRγにのみ結合する (2007)
  • Author(s): 徳永隆俊, 劉暁輝, 岡田浩幸, 松島綾美, 下東康幸
  • Organizer: 第10回環境ホルモン学会研究発表会
  • Year and Date: 20071210-20071211
• [Presentation] Estrogen-related receptorγ(ERRγ) as a special receptor for endocrine disruptor bisphenol A (2007)
  • Author(s): Matsushima, A., Takayanagi, S., Tokunaga, T., Liu, X., Okada, H., Shimohigashi, Y.
  • Organizer: The 27th International Symposium on Halogenated Persistent Organic Pollutants- DIOXIN 2007
  • Place of Presentation: 東京
  • Year and Date: 20070902-20070907
• [Presentation] A strategy to explore the Target Receptor of Endocrine Disruptors, Estrogen-related Receptorγ(ERRγ) as a Genuine Acceptor of Bisphenol A (2007)
  • Author(s): 下東康幸
  • Organizer: 6th World Congress on Alternatives & Animal Use in the Life Sciences
  • Place of Presentation: 東京
  • Year and Date: 20070821-20070825
• [Remarks]
  • URL: http://lsfb.scc.kyushu-u.ac.jp