2009 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 |
Principal Investigator |
岩田 久人 Ehime University, 沿岸環境科学研究センター, 教授 (10271652)
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Co-Investigator(Kenkyū-buntansha) |
石橋 弘志 愛媛大学, 沿岸環境科学研究センター, グローバルCOE准教授 (90403857)
能勢 眞人 愛媛大学, プロテオ医学研究センター, 教授 (70030913)
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Keywords | シトクロムP450 (cytochrome P450) / aryl hydrocarbon receptor(AHR) / constitutive androstane receptor(CAR) / pregnane X receptor(PXR) / Peroxisome proliferator-activated receptor(PPAR) / 感受性 / 化学物質 / persistent organic pollutants(POPs) |
Research Abstract |
本年度得られた成果は、以下の(1)-(4)のように要約できる。 (1)細胞内受容体およびCYPのcDNAクローニング:無脊椎動物・魚類・両生類・鳥類・ほ乳類に属する生物種の細胞内受容体(またはそのホモログ)、およびCYP1-4ファミリーに属する分子種の全長cDNAのクローン化に成功した。また、これまでに報告されてこなかった新規の細胞内受容体・CYP分子種も新たに発見した。(2)CYP遺伝子プロモーター/エンハンサー領域のクローニング:魚類・両生類・鳥類・ほ乳類に属する生物種のCYP遺伝子プロモーター/エンハンサー領域のクローニングに成功した。in silico系およびin vitro系での解析により、細胞内受容体特異的な反応部位を同定することができた。これらの結果により、細胞内受容体-CYPシグナル伝達系の進化および生物種特異性の一端が明らかになった。(3)CYPによる化学物質代謝能の解明と代謝経路・産物の網羅的解析:鳥類・ほ乳類のCYP1A分子種の全長cDNAのクローンを用いて、これら遺伝子のin vitro系による蛋白質の発現に成功した。またエトキシレゾルフィンやPCBなどの化学物質(基質)とこれら蛋白質を反応させることにより、代謝産物を同定することができた。得られた代謝産物の種類・量から、進化学的近縁種であってもCYP1の代謝能は種間で大きく異なることがわかった。(4)細胞内受容体およびCYP以外の感受性規定因子の探索:組換え近交系マウス各系統の脾細胞を2,3,7,8-四塩素化ダイオキシンで処理し、CYP1A1遺伝子発現量の用量依存性を解析したところ、マウス各系統群間でのEC_<50>等の用量一応答パラメーターに明確な差が認められた。これら感受性の差はマウス各系統のAHRアミノ酸配列のみでは説明できなかった。したがって、この差はAHR以外の要因が関与していると推察された。
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Author(s)
Watanabe, M.X., Kunisue, T., Tao, L., Kannan, K., Subramanian, An., Tanabe, S., Iwata, H.
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Environmental Toxicology and Chemistry (in press)
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Kai, H., Ishibashi, Y., Mori, T., Ishibashi, H., Kawaguchi, T., Ohwaki, H., Arizono, K., Takemasa, T.
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Journal Title
Material Recycle and Waste Management Research (in press)
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[Journal Article] Relationship of urinary arsenic metabolites to intake estimates in residents of the Red river delta, Vietnam2009
Author(s)
Agusa, T., Kunito, T., Minh, T.B., Kim Trang, P.T., Iwata, H., Viet, P.H., Tanabe, S.
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Environmental Pollution 157
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Imaeda, D., Kunisue, T., Ochi, Y., Iwata, H., Tsydenova, O., Takahashi, S., Amano, M., Petrov, E.A., Batoev, V.B., Tanabe, S.
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Hirano, M., Ishibashi, H., Kim, J.W., Matsumura, N., Arizono, K.
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[Journal Article] Effects of co-exposure to 2,3,7,8-tetrachlorodihenzo-p-dioxin and perfluorooctane sulfonate or perfluorooctanoic acid on expression of cytochrome P450 isoforms in chicken(Gallus gallus)embryo hepatocyte cultures2009
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Watanabe, M.X., Jones, S.P., Iwata, H., Kim, E.Y., Kennedy, S.W.
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Comparative Biochemistry and Physiology, Part C Toxicology and Pharmacology 149
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[Journal Article] 8-hydroxy-2'-deoxyguanosine(8-OHdG)as a possible marker of arsenic poisoning : A clinical case study on the relationship between concentrations of 8-OHdG and each arsenic compound in urine of an acute promyelocytic leukemia patient being treated with arsenic trioxide2009
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Fujihara, J., Agusa, T., Tanaka, J., Fujii, Y., Moritani, T., Hasegawa, M., Iwata, H., Tanabe, S., Takeshita, H.
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Forensic Toxicology 27
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[Journal Article] Genetic polymorphisms in AS3MT and arsenic metabolism in residents of the red river delta, Vietnam2009
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Agusa, T., Iwata, H., Fujihara, J., Kunito, T., Takeshita, H., Minh, T.B., Trang, P.T., Viet, P.H., Tanabe, S.
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Journal Title
Toxicology and Applied Pharmacology 236
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[Journal Article] Genetic polymorphisms in glutathione S-transferase(GST)superfamily and arsenic metabolism in residents of the Red River Delta, Vietnam2009
Author(s)
Agusa, T., Iwata, H., Fujihara, J., Kunito, T., Takeshita, H., Minh, T.B., Trnag, P.T., Viet, P.H., Tanabe, S.
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Journal Title
Toxicology and Applied Pharmacology 242
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[Journal Article] Human exposure to arsenic from groundwater in the red river and Mekong river deltas in Vietnam2009
Author(s)
Agusa, T., Inoue, S., Kunito, T., Minh, T.B., Ha, N.N., Tu, N.P.C., Kim Trang, P.T., Iwata, H., Viet, P.H., Tuyen, B.C., Tanabe, S.
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International Journal of Environmental Studies 66
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[Journal Article] Acute toxicity of pharmaceutical and personal care products on freshwater crustacean(Thamnocephalus platyurus)and fish(Oryzias latipes)2009
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Kim, J.W., Ishibashi, H., Yamauchi, R., Ichikawa, N., Takao, Y., Hirano, M., Koga, M., Arizono, K.
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Journal Title
The Journal of Toxicological Sciences 34
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[Journal Article] Occurrence of pharmaceutical and personal care products(PPCPs)in surface water from Mankyung River, South Korea2009
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Kim, J.W., Jang, H.S., Kim, J.G., Ishibashi, H., Hirano, M., Nasu, K., Ichikawa, N., Takao, Y., Shinohara, R., Arizono, K.
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Journal of Health Science 55
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[Journal Article] Expression analysis of estrogen-responsive genes vitellogenin 1 and 2 in liver of male medaka(Oryzias latipes)exposed to selective ligands of estrogen receptor subtypes2009
Author(s)
Yamaguchi, A., Ishibashi, H., Kohra, S., Arizono, K., Kato, K., Nakahama, T., Kanno, Y., Inouye, Y., Tominaga, N.
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Journal Title
Journal of Health Science 55
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[Journal Article] Aneurysms of the renal arteries associated with segmental arterial mediolysis in a case of polyarteritis nodosa2009
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Soga, Y., Nose, M., Arita, N., Komor, H., Miyazaki, T., Maeda, T., Furuya, K.
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[Journal Article] Charactrization of lymphangiogenesis in various stages of idiopathic diffuse alveolar damage2009
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Yamashita, M., Iwama, N., Date, F., Chiba, R., Ebina, M., Miki, H., Yamauchi, K., Sawai, T., Nose, M., Sato, S., Takahashi, T., Ono, M.
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[Journal Article] Genetic dissociation of dacryoadenitis and sialadenitis in a sjogren's syndrome mouse model with common and different susceptibility gene loci2009
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Kamao, T., Miyazaki, T., Soga, Y., Komori, H., Terada, M., Ohashi, Y., Nose, M.
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[Journal Article] Hexabromocyclododecanes in human adipose tissue from Japan2009
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Tanaka, Y., Komori, H., Mori, S., Soga, Y., Tsubaki, T., Terada, M., Miyazaki, T., Fujino, T., Nakamura, S., Kanno, H., Sawasaki, T., Endo, Y., Nose, M.
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[Presentation] Arsenic, manganese and barium contamination in groundwater and human in Vietnam2010
Author(s)
Agusa, T., Inoue, S., Kunito, T., Minh, T.B., Tu, N.P.C., Ha, N.N., Kim Trang, P.T., Iwata, H., Tuyen, B.C., Viet, P.H., Tanabe, S.
Organizer
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Place of Presentation
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Year and Date
20100301-20100305
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[Presentation] Development of an in vitro reporter gene assay for screening the ecdysone receptor agonists in mysid crustacean, Americamysis bahia2009
Author(s)
Hirano, M., Ishibashi, H., Kim, E.Y., Arizono, K., Iwata, H.
Organizer
第12回日本内分泌撹乱化学物質学会
Place of Presentation
東京、日本
Year and Date
20091207-20091208
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[Presentation] Association of inorganic arsenic metabolism with genetic polymorphisms of GST isoforms in North Vietnamese populations : Utilization of stored samples in the environmental specimen bank of Ehime University2009
Author(s)
Agusa, T., Iwata, H., Fujihara, J., Kunito, T., Takeshita, H., Minh, T.B., Kim Trang, P.T., Viet, P.H., Tanabe, S.
Organizer
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Place of Presentation
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Year and Date
20091203-20091205
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[Presentation] Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on peripheral nervous system in developing red seabream(Pugrus major)embryos2009
Author(s)
Iida, M., Kim, E.Y., Murakami, Y., Shima, Y., Iwata, H.
Organizer
International Symposium on Environmental Specimen Bank, Exploring Possibility of Setting-up ESBs in Developing Countries
Place of Presentation
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Year and Date
20091203-20091205
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[Presentation] Moleculaz cloning of the ecdysone receptor from a mysid crustacean(Americamysis bahia)and development of an in vitro reporter gene assay to detect the receptor-mediated responses by chemicals2009
Author(s)
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Organizer
International Symposium on Environmental Specimen Bank, Exploring Possibility of Setting-up ESBs in Developing Countries
Place of Presentation
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Year and Date
20091203-20091205
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[Presentation] Effects of dioxin-like and perfluorinated compounds on hepatic cytochrome P450 and plasma hormones in pigs from an indian open waste dumping site2009
Author(s)
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Organizer
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Place of Presentation
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Year and Date
20091203-20091205
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[Presentation] Intracellular localization of the AHR2 isoform from avian species2009
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Organizer
International Symposium on Environmental Specimen Bank, Exploring Possibility of Setting-up ESBs in Developing Countries
Place of Presentation
Matsuyama, Japan
Year and Date
20091203-20091205
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[Presentation] Functional characterization of AHR isoforms, AHR1, AHR2 and AHRR in avian species2009
Author(s)
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Organizer
21^<st> Century Advances in the Molecular Toxicology of Environmental Chemicals and Pathogenesis of Disease
Place of Presentation
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Year and Date
20091026-20091027
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[Presentation] Characterization of ecdysone receptor and ultraspiracle mRNA through molting period in mysid crustacean2009
Author(s)
Hirano, M., Ishibashi, H., Yamauchi, R., Kim, J.W., Arizono, K.
Organizer
21^<st> Century Advances in the Molecular Toxicology of Environmental Chemicals and Pathogenesis of Disease
Place of Presentation
Tokyo, Japan
Year and Date
20091026-20091027
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[Presentation] Transcriptional modulation of estrogen-responsive genes in male medaka(Oryzias latipes)after exposure to synthetic polycyclic musks2009
Author(s)
Ishibashi, H., Yamauchi, R., Kim, J.W., Hirano, M., Mori, T., Tominaga, N., Arizono, K.
Organizer
21^<st> Century Advances in the Molecular Toxicology of Environmental Chemicals and Pathogenesis of Disease
Place of Presentation
Tokyo, Japan
Year and Date
20091026-20091027
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[Presentation] Characterization of aryl hydrocarbon receptor in avian species2009
Author(s)
Fujisawa, N., Tanaka, K., Yamamoto, H., Ikenaka, Y., Kim, E.Y., Lee, J.S., Iwata, H., Ishizuka, M.
Organizer
21^<st> Century Advances in the Molecular Toxicology of Environmental Chemicals and Pathogenesis of Disease
Place of Presentation
Tokyo, Japan
Year and Date
20091026-20091027
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[Presentation] Interindividual variation in arsenic metabolism in a Vietnamese population : association with single nucleotide polymorphisms in AS3MT2009
Author(s)
Agusa, T., Iwata, H., Fujihara, J., Kunito, T., Takeshita, H., Minh, T.B., Kim, P.T., Viet, P.H., Tanabe, S.
Organizer
BIOLOGICAL RESPONSES TO CHEMICAL CONTAMINANTS : from molecular to community level Interdisciplinary Symposium for Young Investigators
Place of Presentation
Aveiro, Portugal
Year and Date
20090902-20090904
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