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Elucidation on pathophysiological significance of orphan P450 expression in tumor tissue and its application to drug discovery research

Research Project

Project/Area Number 25293128
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Applied pharmacology
Research InstitutionNational Institute of Health Sciences

Principal Investigator

Maekawa Keiko  国立医薬品食品衛生研究所, 医薬安全科学部, 室長 (70270626)

Co-Investigator(Kenkyū-buntansha) 谷内田 真一  国立研究開発法人国立がん研究センター, がんゲノミクス研究分野, ユニット長 (20359920)
斎藤 嘉朗  国立医薬品食品衛生研究所, 医薬安全科学部, 部長 (50215571)
安達 基泰  国立研究開発法人量子科学技術研究開発機構, 東海量子ビーム応用研究センター, 上席研究員 (60293958)
Project Period (FY) 2013-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2015: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2014: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2013: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Keywords酸化還元酵素 / 癌 / 生理活性 / 酵素
Outline of Final Research Achievements

This study aimed to clarify 1) functional and structural characteristics of orphan P450s, CYP2U1, CYP4X1, and CYP4Z1, and 2) their pathophysiological roles in tumor tissues. In E. coli expression systems, recombinant orphan P450 enzymes were present as P420 apoenzymes not as P450 holoenzymes, and further examination is necessary to find out optimal N-terminal modifications and expression conditions. We started to explore endogenous substrates of CYP2U1 expressed by baculovirus-silkworm expression systems. Highly expressed CYP4Z1 mRNA in breast cancer tissues were significantly correlated with several oxidative fatty acid levels, suggesting important roles of CYP4Z1 on tumor growth and progression.

Report

(5 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (13 results)

All 2016 2015 2014 Other

All Int'l Joint Research (2 results) Journal Article (3 results) (of which Open Access: 2 results,  Acknowledgement Compliant: 1 results,  Peer Reviewed: 2 results) Presentation (8 results) (of which Int'l Joint Research: 2 results)

  • [Int'l Joint Research] University of Connecticut(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] U of Connecticut, School of Pharmacy(米国)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Crystal structure analysis of human drug metabolizing enzyme CYP2C9 complexed with medicinal compound Losartan.2016

    • Author(s)
      Adachi M, Matsuzawa Y, Kuroki R, Saito Y and Maekawa K
    • Journal Title

      Photon Factory Activity Report

      Volume: 33 Pages: 364-364

    • Related Report
      2016 Annual Research Report
    • Open Access / Acknowledgement Compliant
  • [Journal Article] Cross-Classification of Human Urinary Lipidome by Sex, Age, and Body Mass Index.2016

    • Author(s)
      Okemoto K, Maekawa K, Tajima Y, Tohkin M, Saito Y
    • Journal Title

      PLoS One

      Volume: 11 Issue: 12 Pages: e0168188-e0168188

    • DOI

      10.1371/journal.pone.0168188

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 薬物相互作用に影響を及ぼす遺伝子多型とその人種差2014

    • Author(s)
      前川京子, 佐井君江
    • Journal Title

      ファルマシア

      Volume: 50(7) Pages: 669-673

    • NAID

      130005245880

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Presentation] Crystal Structures of CYP2C9, CYP2C9*3 and CYP2C9*30 in Complex with Multiple Losartan Molecules Reveal a Peripheral Binding Site and Alternate Active Site Orientations.2016

    • Author(s)
      Maekawa K, Adachi M, Matsuzawa Y, Kuroki R, Saito Y, Shah M
    • Organizer
      The 21st International Symposium on Microsomes and Drug Oxidations (MDO2016)
    • Place of Presentation
      UC Davis Conference Center, Davis, California, USA
    • Year and Date
      2016-10-02
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Orphan P450 expression and oxidative fatty acid metabolite levels in breast cancer2016

    • Author(s)
      Keiko Maekawa, Yumiko Matsuzawa, Yoshiro Saito, Shin-ichi Yachida
    • Organizer
      日本薬理学会89回年会
    • Place of Presentation
      パシフッコ横浜
    • Year and Date
      2016-03-10
    • Related Report
      2015 Annual Research Report
  • [Presentation] ヒト由来薬物代謝酵素CYP2C9の一塩基置換体(*3および*30)と抗高血圧薬ロサルタンとの複合体のX線結晶構造解析2015

    • Author(s)
      安達 基泰, 黒木 良太、前川 京子, 松澤 由美子, 斎藤 嘉朗
    • Organizer
      BMB2015(第 38回日本分子生物学会年会、第 88回日本生化学会大会 合同大会)
    • Place of Presentation
      神戸ポートピアホテル
    • Year and Date
      2015-12-04
    • Related Report
      2015 Annual Research Report
  • [Presentation] Purification of cytochrome P450 2C9.1, 2C9.3 and 2C9.30 expressed in E. coli and their activities toward arachidonic acid in vitro2015

    • Author(s)
      Keiko Maekawa, Yumiko Matsuzawa, Motoyasu Adachi, Ryota Kuroki and Yoshiro Saito
    • Organizer
      19th International Conference on Cytochrome P450
    • Place of Presentation
      Tokyo
    • Year and Date
      2015-06-12 – 2015-06-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] Purification of cytochrome P450 2C9.1, 2C9.3 and 2C9.30 expressed in E. coli and their activities toward arachidonic acid in vitro2015

    • Author(s)
      Keiko Maekawa, Yumiko Matsuzawa, Motoyasu Adachi, Ryota Kuroki, Yoshiro Saito
    • Organizer
      19th International Conference on Cytochrome P450
    • Place of Presentation
      National Olympics Memorial Youth Center, Shibuya-ku, Tokyo
    • Year and Date
      2015-06-12
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] X線結晶回折法によるヒト由来薬物代謝酵素CYP2C9および一塩基置換体(*30)と抗高血圧薬ロサルタンの相互作用解析2014

    • Author(s)
      安達 基泰, 前川 京子, 松澤 由美子, 斎藤 嘉朗, 黒木 良太
    • Organizer
      第14回日本蛋白質科学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2014-06-25 – 2014-06-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] バイオマーカー探索・検証のためのヒト血液中脂質代謝物レベルに関する網羅的検討

    • Author(s)
      前川京子, 石川将己, 妹尾勇弥, 田島陽子, 齊藤公亮, 浦田政世, 村山真由子,熊谷雄治, 斎藤嘉朗
    • Organizer
      日本薬物動態学会第28回年会
    • Place of Presentation
      タワーホール船堀
    • Related Report
      2013 Annual Research Report
  • [Presentation] 動物モデルを用いた医薬品化合物によるリン脂質症の解析

    • Author(s)
      前川 京子、齊藤 公亮、山田 弘、斎藤 嘉朗
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本大学黒髪キャンパス
    • Related Report
      2013 Annual Research Report

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Published: 2013-05-21   Modified: 2022-02-16  

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