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Species differences and evolution of phase II conjugation reaction and its cellular function

Research Project

Project/Area Number 15K12213
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Risk sciences of radiation and chemicals
Research InstitutionHokkaido University

Principal Investigator

Ikenaka Yoshinori  北海道大学, 獣医学研究科, 准教授 (40543509)

Co-Investigator(Kenkyū-buntansha) 水川 葉月  北海道大学, 獣医学研究科, 助教 (60612661)
中山 翔太  北海道大学, 獣医学研究科, 助教 (90647629)
Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords異物代謝第II相抱合反応 / グルクロン酸 / UGT / 生物種差 / 細胞内デリバリー
Outline of Final Research Achievements

UGTs are among the most important xenobiotic metabolizing enzymes that conjugate a wide range of endogenous and exogenous compounds. Previous studies showed that Felidae species and Pinnipedia species have very low UGT activities toward some phenolic compounds because of the UGT1A6 pseudogene and small numbers of UGT1A isozymes. In addition to the UGT1As, UGT2Bs isozymes also conjugate various endogenous and exogenous compounds. Results of UGT activity measurement indicated cats and pinniped species had very low activities toward these substrates. Furthermore, Felidae species had the same nonsense mutation in UGT2B, which suggested that Felidae UGT2B31 was also a pseudogene in addition to UGT1A6. Together with the lower activity of UGT1As, these findings of lower activity of UGT2B suggested that Felidae and some pinniped species have very low UGT activity toward a wide range of chemicals.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (27 results)

All 2017 2016 2015 Other

All Int'l Joint Research (3 results) Journal Article (11 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 11 results,  Open Access: 5 results,  Acknowledgement Compliant: 11 results) Presentation (11 results) (of which Int'l Joint Research: 2 results,  Invited: 4 results) Remarks (2 results)

  • [Int'l Joint Research] カセサート大学(タイ)

    • Related Report
      2015 Research-status Report
  • [Int'l Joint Research] ザガジグ大学(エジプト)

    • Related Report
      2015 Research-status Report
  • [Int'l Joint Research] ヨハネスブルグ大学/ノースウェスト大学(南アフリカ)

    • Related Report
      2015 Research-status Report
  • [Journal Article] Characterization of Species Differences in Xenobiotic Metabolism in Non-experimental Animals2017

    • Author(s)
      水川葉月、池中良徳、筧麻友、中山翔太、石塚真由美
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 137 Issue: 3 Pages: 257-263

    • DOI

      10.1248/yakushi.16-00230-2

    • NAID

      130005396880

    • ISSN
      0031-6903, 1347-5231
    • Year and Date
      2017-03-01
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The African hedgehog (Atelerix albiventris): low phase I and phase II metabolism activities.2016

    • Author(s)
      Saengtienchai A, Ikenaka Y, Bortey-Sam N, Jermnark U, Mizukawa H, Kawai YK, Nakayama SMM, Ishizuka M.
    • Journal Title

      Comp Biochem Physiol C Pharmacol Toxicol.

      Volume: 190 Pages: 38-47

    • DOI

      10.1016/j.cbpc.2016.08.005

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Characterization of Equine Cytochrome P450: Role of CYP3A in the Metabolism of Diazepam2016

    • Author(s)
      Nakayama SMM, Ikenaka Y, Hayami A, Mizukawa H, Darwish WS, Watanabe KP, Kawai YK, Ishizuka M
    • Journal Title

      Journal of Veterinary Pharmacology and Therapeutics

      Volume: in press Issue: 5 Pages: 478-87

    • DOI

      10.1111/jvp.12303

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] β-carotene and retinol contents in the meat of herbivorous ungulates with a special reference to their public health importance2016

    • Author(s)
      Darwish WS, Ikenaka Y, Morshdy AE, Eldesoky KI, Nakayama SMM, MizukawaH, Ishizuka M.
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 78 Issue: 2 Pages: 351-354

    • DOI

      10.1292/jvms.15-0287

    • NAID

      130005131329

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Cytochrome P450-mediated warfarin metabolic ability is not a critical determinant of warfarin sensitivity in avian species: In vitro assays in several birds and in vivo assays in chicken2015

    • Author(s)
      Watanabe KP, Kawata M, Ikenaka Y, Nakayama SMM, Ishii C, Darwish WS, Saengtienchai A, Mizukawa H, Ishizuka M
    • Journal Title

      Environ Toxicol Chem

      Volume: 34 Issue: 10 Pages: 2328-2334

    • DOI

      10.1002/etc.3062

    • NAID

      120005906927

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Uridine diphosphate-glucuronosyltransferase (UGT) xenobiotic metabolizing activity and genetic evolution in Pinniped species2015

    • Author(s)
      Kakehi M, Ikenaka Y, Nakayama SMM, Kawai YK, Watanabe KP, Mizukawa H, Nomiyama K, Tanabe S, Ishizuka M
    • Journal Title

      Tox Sci

      Volume: 147 Pages: 360-369

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Metabolic Activation of Heterocyclic Amines and Expression of Xenobiotic-Metabolizing Enzymes in the Gastrointestinal Tract of Rats2015

    • Author(s)
      Darwish WS, Nakayama SMM, Itotani Y, Ohno M, Ikenaka Y, Ishizuka M
    • Journal Title

      J Food Sci

      Volume: 22 Issue: 7 Pages: 1719-1726

    • DOI

      10.1111/1750-3841.12931

    • NAID

      120005768777

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Characterization and tissue distribution of conjugated metabolites of pyrene in the rat2015

    • Author(s)
      Saengtienchai A, Ikenaka Y, Darwish WS, Nakayama SMM, Mizukawa H, Ishizuka M
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 77 Issue: 10 Pages: 1261-1267

    • DOI

      10.1292/jvms.14-0632

    • NAID

      130005107595

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Are red gourami (Colisa labiosa) low xenobiotic metabolizers? Elucidation of in vivo pharmacokinetics of pyrene as a model substrate2015

    • Author(s)
      Ikenaka Y, Nakayama SMM, Oguri M, Saengtienchai A, Mizukawa H, Kobayashi J, Darwish WS, Ishizuka M
    • Journal Title

      Environ Toxicol Pharmacol

      Volume: 39 Issue: 3 Pages: 1148-1153

    • DOI

      10.1016/j.etap.2015.04.004

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Partial cloning of CYP2C23a genes and hepatic protein expression in eight representative avian species2015

    • Author(s)
      Watanabe KP, Kawai YK, Nakayama SMM, Ikenaka Y, Mizukawa H, Takaesu N, Ito M, Ikushiro S, Sakaki T, Ishizuka M
    • Journal Title

      Journal of Veterinary Pharmacology and Therapeutics

      Volume: 38 Issue: 2 Pages: 190-195

    • DOI

      10.1111/jvp.12159

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Identification of inter-specific differences in phase II reactions: Determination of metabolites in the urine of 16 mammalian species exposed to environmental pyrene.2015

    • Author(s)
      Saengtienchai A, Ikenaka Y, Nakayama SMM, Mizukawa H, Kakehi M, Bortey-Sam N, Darwish W, Tsubota T, Terasaki M, Poapolathep A, Ishizuka M
    • Journal Title

      Environmental Toxicology and Chemistry

      Volume: 33 Issue: 9 Pages: 2062-2069

    • DOI

      10.1002/etc.2656

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 代謝酵素の動物種差2017

    • Author(s)
      石塚真由美、中山翔太、水川葉月、池中良徳
    • Organizer
      日本薬学会第137年会シンポジウム
    • Place of Presentation
      仙台国際センター、仙台市
    • Year and Date
      2017-03-24
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] UGT2Bサブファミリーに着目した食肉目におけるグルクロン酸抱合能の動物種差解明2016

    • Author(s)
      近藤誉充、池中良徳、中山翔太、水川葉月、Aksorn Saengtienchai、Yared Beyene、坂本健太郎、和田昭彦、服部薫、三谷曜子、田辺信介、野見山桂、石塚真由美
    • Organizer
      平成28年度内外環境応答・代謝酵素研究会
    • Place of Presentation
      静岡県立大学薬学部、静岡市、静岡県
    • Year and Date
      2016-09-17
    • Related Report
      2016 Annual Research Report
  • [Presentation] 鳥類におけるグルクロン酸抱合酵素による薬物代謝2016

    • Author(s)
      新屋惣、池中良徳、中山翔太、石井千尋、水川葉月、齊藤慶輔、渡邉有希子、伊藤真輝、高江洲昇、坂本健太郎、石塚真由美
    • Organizer
      第22回日本野生動物医学会
    • Place of Presentation
      宮崎市民プラザ、宮崎市
    • Year and Date
      2016-09-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] 野生動物及び実験動物におけるグルクロン酸抱合酵素の動物種差解明2016

    • Author(s)
      近藤誉充、池中良徳、中山翔太、水川葉月、Aksorn Saengtienchai、Yared Beyene、坂本健太郎、和田昭彦、服部薫、三谷曜子、田辺信介、野見山桂、石塚真由美
    • Organizer
      第159回日本獣医学会学術集会
    • Place of Presentation
      日本大学生物資源科学部、藤沢市、神奈川県
    • Year and Date
      2016-09-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] ハリネズミは化学物質高感受性種? African hedgehog (Atalerix albiventris)で観察された低薬物代謝能2016

    • Author(s)
      アクソルン サエンティエンチャイ、池中 良徳、ネスタ サム、ウスマ ジャムナーク、水川 葉月、中山 翔太、石塚 真由美
    • Organizer
      第43回日本毒性学会学術年会
    • Place of Presentation
      ウインクあいち、名古屋市
    • Year and Date
      2016-06-29
    • Related Report
      2016 Annual Research Report
  • [Presentation] How to identify the high sensitive species to chemicals? ~Development of screening methods of phase II xenobiotic metabolism~.2016

    • Author(s)
      Yoshinori Ikenaka
    • Organizer
      Second international veterinary medicine conference entitles: Role of veterinary medicine in development of animal wealth and human health safety
    • Place of Presentation
      Suez, Egypt
    • Year and Date
      2016-03-15
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] “バイオハザードコントロール”における“ケミカルハザード”~他分野連携における環境毒性学の重要性~2015

    • Author(s)
      池中良徳
    • Organizer
      環境ホルモン学会第18回研究発表会
    • Place of Presentation
      自治医科大学、栃木
    • Year and Date
      2015-12-10
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Phase II xenobiotic metabolizm in carnivora -UGT activity and genomestructure in Pinniped species2015

    • Author(s)
      Yoshinori Ikenaka, Mayu Kakehi, Shouta Nakayama, Hazuki Mizukawa, Mayumi Ishizuka
    • Organizer
      7th SETAC Africa Conference
    • Place of Presentation
      Langebaan, South Africa
    • Year and Date
      2015-10-05
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Phase II酵素の欠損動物と非欠損動物ー新たな動物種マッピングー2015

    • Author(s)
      池中良徳, Aksorn Saengtienchai, 筧麻友, Wageh Sobhy Darwish, 水川葉月,中山翔太, 石塚真由美
    • Organizer
      第42回日本毒性学会
    • Place of Presentation
      金沢市、石川県
    • Year and Date
      2015-06-29
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 第II相抱合反応の種差:食肉目におけるグルクロン酸抱合酵素の進化と遺伝子構造2015

    • Author(s)
      池中良徳、筧麻友、中山翔太、川合佑典、渡邊研右、水川葉月、野見山桂、田辺信介、石塚真由美
    • Organizer
      第24回環境化学討論会
    • Place of Presentation
      札幌コンベンションセンター、北海道
    • Year and Date
      2015-06-24
    • Related Report
      2015 Research-status Report
  • [Presentation] ウマにおけるシトクロムP450の特性評価:ジアゼパム代謝を担うCYP3Aの重要性2015

    • Author(s)
      水川葉月、中山翔太、池中良徳、速水秋、Wageh Sobhy Darwish、渡邊研右、川合佑典、石塚真由美
    • Organizer
      第24回環境化学討論会
    • Place of Presentation
      札幌コンベンションセンター、北海道
    • Year and Date
      2015-06-24
    • Related Report
      2015 Research-status Report
  • [Remarks] 北海道大学 大学院獣医学研究院 毒性学教室ホームページ

    • URL

      http://tox.vetmed.hokudai.ac.jp/

    • Related Report
      2016 Annual Research Report
  • [Remarks] 北海道大学大学院獣医学研究科毒性学教室HP

    • URL

      http://tox.vetmed.hokudai.ac.jp/

    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2022-02-22  

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