2013 Fiscal Year Annual Research Report
化学物質による細胞内受容体―異物代謝酵素シグナル伝達系撹乱の感受性支配因子の解明
| Project/Area Number |
21221004
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| Research Institution | Ehime University |
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Principal Investigator |
岩田 久人 愛媛大学, 沿岸環境科学研究センター, 教授 (10271652)
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| Co-Investigator(Kenkyū-buntansha) |
阿草 哲郎 愛媛大学, 沿岸環境科学研究センター, 特任助教 (50403853)
宮崎 龍彦 岐阜大学, 医学部附属病院, 教授 (80239384)
鈴木 賢一 広島大学, 理学(系)研究科(研究院), 特任助教 (90363043)
石橋 弘志 尚絅大学短期大学部, 食物栄養学科, 准教授 (90403857)
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| Project Period (FY) |
2009-05-11 – 2014-03-31
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| Keywords | 化学物質 / 細胞内受容体 / 異物代謝酵素 / 感受性 |
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| Research Abstract |
これまでに本研究課題で構築してきたin vitro CYP誘導レポーター遺伝子アッセイ・SPRアッセイ・FRETアッセイ系を利用して、今年度はより多くの化学物質のスクリーニングを試みた。これらのアッセイによって得られた化学物質と細胞内受容体との相互作用については、50％影響濃度（EC50）やCYP誘導等価係数（IEF）を指標にして評価した。さらに、野生鳥類（カワウ・アホウドリ）・哺乳類（アザラシ）を対象に、in vitro CYP誘導アッセイ系を用いて得られた化学物質の用量-応答曲線と各野生個体群の肝臓での化学物質蓄積量とCYP発現量の関係は一致することが明らかとなった。以上の結果より、in vitro CYP誘導アッセイ系を適用することにより、種特異的感受性を考慮した野生個体群のリスクが評価できることを立証した。
また、鳥類や陸棲・水棲哺乳類の肝ミクロソームに由来するCYPの包括的なin vitro代謝実験系を確立した。これにより、PCB・エストロジェンの代謝物の同定・定量をおこなった。各CYP分子種の代謝力については、in vitro代謝実験とin silico基質-CYP結合モデルから評価し、種特異的な代謝力を規定するアミノ酸残基を特定することができた。
この他、ダイオキシン類曝露に対して敏感な系統マウスと鈍感な系統マウスでAHRと相互作用するタンパク質に質的・量的な差異があるかどうかについて、pull-down法とMALDI-TOF/TOF質量分析法を組み合わせた実験系で検証した。その結果、感受性を規定する候補タンパク質の同定に成功した。その候補タンパク質をin vitro CYP誘導アッセイ系で強制発現させ、ダイオキシン類曝露に対するAHR依存的な反応を測定したところ、感受性が変化することを確認した。したがって、本候補タンパク質は感受性規定因子であると結論された。
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| Current Status of Research Progress |
Reason
25年度が最終年度であるため、記入しない。
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| Strategy for Future Research Activity |
25年度が最終年度であるため、記入しない。
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Research Products
(61 results)
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[Journal Article] Targeted mutagenesis of multiple and paralogous genes in Xenopus laevis using two pairs of transcription activator-like effector nucleases2014
Author(s)
Sakane, Y., Sakuma, T., Kashiwagi, K., Kashiwagi, A., Yamamoto, T. and Suzuki, K. T.
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Journal Title
Dev Growth Differ
Volume: 56(1)
Pages: 108-114
DOI
Peer Reviewed
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[Journal Article] Human exposure to arsenic from drinking water in Vietnam2014
Author(s)
Agusa, T., Trang, P. T. K., Lan, V. M., Anh, D. H., Tanabe, S., Viet, P. H. and Berg, M.
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Journal Title
Science of the Total Environment
Volume: in press
Pages: in press
DOI
Peer Reviewed
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[Journal Article] Molecular and functional characterization of a novel aryl hydrocarbon receptor isoform, AHR1β, in the chicken (Gallus gallus)2013
Author(s)
Lee, J. S., Iwabuchi, K., Nomaru, K., Nagahama, N., Kim, E. Y. and Iwata, H.
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Journal Title
Toxicological Sciences
Volume: 136(2)
Pages: 450-466
DOI
Peer Reviewed
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[Journal Article] Molecular evaluation of a new highly sensitive aryl hydrocarbon receptor in ostriches2013
Author(s)
Fujisawa, N., Darwish, W. S., Ikenaka, Y., Kim, E. Y., Lee, J. S., Iwata, H., Nakayama, S. and Ishizuka, M.
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Journal Title
Poultry Science
Volume: 92(7)
Pages: 1921-1929
DOI
Peer Reviewed
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[Journal Article] Quantitative analysis of the interaction of constitutive androstane receptor with chemicals and steroid receptor coactivator 1 using surface plasmon resonance biosensor systems: a case study of the Baikal seal and the mouse2013
Author(s)
Dau, P. T., Sakai, H., Hirano, M., Ishibashi, H., Tanaka, Y., Kameda, K., Fujino, T., Kim, E. Y. and Iwata, H.
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Journal Title
Toxicological Sciences
Volume: 131(1)
Pages: 116-127
DOI
Peer Reviewed
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[Journal Article] Toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the peripheral nervous system of developing red seabream (Pagrus major)2013
Author(s)
Iida, M., Kim, E. Y., Murakami, Y., Shima, Y. and Iwata, H.
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Journal Title
Aquatic Toxicology
Volume: 128-129
Pages: 193-202
DOI
Peer Reviewed
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[Journal Article] Toxicokinetics of dioxins and other organochlorine compounds in Japanese people: association with hepatic CYP1A2 expression levels2013
Author(s)
Watanabe, M. X., Kunisue, T., Ueda, N., Nose, M., Tanabe, S. and Iwata, H.
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Journal Title
Environment international
Volume: 53
Pages: 53-61
DOI
Peer Reviewed
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[Journal Article] Sedimentary records of metal depositions in Japanese alpine lakes for the last 250 years: recent enrichments of airborne Sb and In in East Asia2013
Author(s)
Kuwae, M., Tsugeki, N. K., Agusa, T., Toyoda, K., Yukinori, T., Ueda, S., Tanabe, S. and Urabe, J.
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Journal Title
Science of the Total Environment
Volume: 442
Pages: 189-197
DOI
Peer Reviewed
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[Journal Article] Exposure assessment of lead to workers and children in the battery recycling craft village, Dong Mai, Vietnam2013
Author(s)
Noguchi, T., Itai, T., Tue, N. M., Agusa, T., Ha, N. N., Horai, S., Trang, P. T. K., Viet, P. H., Takahashi, S. and Tanabe, S.
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Journal Title
Journal of Material Cycles and Waste Management
Volume: 16(1)
Pages: 46-51
DOI
Peer Reviewed
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[Journal Article] A bacterial artificial chromosome transgene with polymorphic Cd72 inhibits the development of glomerulonephritis and vasculitis in MRL-Faslpr lupus mice2013
Author(s)
Oishi, H., Tsubaki, T., Miyazaki, T., Ono, M., Nose, M. and Tahahashi, S.
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Journal Title
Journal of Immunology
Volume: 190
Pages: 2129-2137
DOI
Peer Reviewed
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[Journal Article] Study of dietary phytoestrogens and estrogenic activity in pet animal diets2013
Author(s)
Nakashima, S., Ji, H., Ishitobi, S., Kawazoe, S., Koga, M., Shinohara, R., Ishibashi, H., Tominaga, N. and Arizono, K.
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Journal Title
Japanese Journal of Food Chemistry and Safety
Volume: 20(1)
Pages: 22-30
Peer Reviewed
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[Presentation] Characterization of mercury binding proteins in the liver of northern fur seals (Callorhinus ursinus)2014
Author(s)
Agusa, T., Yasugi, S., Ikemoto, T., Kunito, T., Baba, N., Tanabe, S. and Iwata, H.
Organizer
The Society of Toxicology (SOT) 53rd Annual Meeting
Place of Presentation
Phoenix, USA
Year and Date
20140323-20140327
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[Presentation] ベトナム人におけるAS3MT遺伝子の発現量とSNPsの関係2013
Author(s)
阿草哲郎, 國頭 恭, Nguyen Minh Tue, Vi, T. M. Lan, Tu, B. Minh, Pham, T. K. Trang, 藤原純子, 竹下治男, 高橋 真, Pham, H. Viet, 田辺信介, 岩田久人
Organizer
第19回ヒ素シンポジウム
Place of Presentation
福岡
Year and Date
20131116-20131117
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[Presentation] Effect of aryl hydrocarbon receptor variants and hnRNPA2/B1 on dioxin-induced cyp1a1 transactivation in MRL/lpr and C3H/lpr2013
Author(s)
Cho, S. W., Suzuki, K. I., Miura, Y., Watanabe, M., Miyazaki, T., Nose, M., Iwata, H. and Kim, E. Y.
Organizer
The 33rd International Symposium on Halogenated Persistent Organic Pollutants (DIOXIN2013)
Place of Presentation
Daegu, Korea
Year and Date
20130825-20130830
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[Presentation] Thyroid hormone-mediated effects of dioxins in wild Baikal seals (Pusa sibirica)2013
Author(s)
Iwata, H, Hirakawa, S., Eguchi, A., Imaeda, D., Kunisue, T., Kim, E. Y., Kannan, K., Petrov, E. A., Batoev, V. B. and Tanabe, S.
Organizer
The 33rd International Symposium on Halogenated Persistent Organic Pollutants (DIOXIN2013)
Place of Presentation
Daegu, Korea
Year and Date
20130825-20130830
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[Presentation] Polychlorinated biphenyls and their hydroxylated metabolites (OH-PCBs) in the Baikal seals and implication from a toxicogenomic approach2013
Author(s)
Nomiyama, K., Eguchi, A., Hirakawa, S. Kanbara, C., Imaeda, D., Kim, E. Y., Iwata, H. and Tanabe, S.
Organizer
The 33rd International Symposium on Halogenated Persistent Organic Pollutants (DIOXIN2013)
Place of Presentation
Daegu, Korea
Year and Date
20130825-20130830
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[Presentation] Functional characterization of aryl hydrocarbon receptor from the polar bear (Ursus maritimus)2013
Author(s)
Hwang, J. H., Jeong, L. R., Kannan, K., Evans, T. J., Iwata, H. and Kim, E. Y.
Organizer
The 33rd International Symposium on Halogenated Persistent Organic Pollutants (DIOXIN2013)
Place of Presentation
Daegu, Korea
Year and Date
20130825-20130830
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[Presentation] Identification of quantitative trait loci (QTL) associated with inorganic arsenic metabolism using recombinant inbred strains of mice2013
Author(s)
Agusa, T., Komori, H., Soga, Y., Nose, M., Mori, S., Kubota, R., Tanabe, S. and Iwata, H.
Organizer
The XIII International Congress of Toxicology 2013
Place of Presentation
Seoul, Korea
Year and Date
20130630-20130704
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[Presentation] Identification and functional characterization of a novel chicken aryl hydrocarbon receptor isoform, 2nd AHR12013
Author(s)
Lee, J. S., Iwabuchi, K., Nomaru, K., Nagahama, N., Kim, E. Y. and Iwata, H.
Organizer
The XIII International Congress of Toxicology 2013
Place of Presentation
Seoul, Korea
Year and Date
20130630-20130704
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[Presentation] Effects of aryl hydrocarbon receptor and transcriptional co-factor(s) on transactivation in MRL/lpr and C3H/lpr mouse strains2013
Author(s)
Cho, S. W., Kim, E. Y., Suzuki, K., Miura, Y., Iwata, H., Miyazaki, T. and Nose, M.
Organizer
The XIII International Congress of Toxicology 2013
Place of Presentation
Seoul, Korea
Year and Date
20130630-20130704
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[Presentation] Transcriptomic analysis of the liver of Japanese medaka (Oryzias latipes) exposed to Kanechlor-500, BDE47 or PFOS2013
Author(s)
Ishibashi, H., Uchida, M., Hirano, M., Kobayashi, J., Komorita, T., Nakamura, H., Kagami, Y., Kusano, T., Ishibashi, Y. and Arizono, K.
Organizer
7th International Conference on Marine Pollution and Ecotoicology
Place of Presentation
Hong Kong
Year and Date
20130617-20130621
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[Presentation] Arsenic exposure and susceptibility in Vietnamese
Author(s)
Agusa, T., Kunito, T., Inoue, S., Minh, T. B., Tue, N. M., Ha, N. N., Tu, N. P C., Trang, P. T. K., Fujihara, J., Takeshita, H., Takahashi, S. Tuyen, B. C., Viet, P. H., Iwata, H. and Tanabe, S.
Organizer
NIES Arsenic Workshop 2013 -Seeking ways to reduce the arsenic health hazards from the toxicological standpoint-
Place of Presentation
つくば
Invited
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