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Naphthalens that covalently bind to macromolecules contaminated in the atmosphere in southern California

Research Project

Project/Area Number 18406003
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section海外学術
Research Field Environmental pharmacy
Research InstitutionUniversity of Tsukuba

Principal Investigator

KUMAGAI Yoshito  University of Tsukuba, 大学院・人間総合科学研究科, 教授 (00250100)

Co-Investigator(Kenkyū-buntansha) SUMI Daigo  筑波大学, 大学院・人間総合科学研究科, 准教授 (30400683)
山野 茂  福岡大学, 薬学部, 准教授 (80140755)
高野 裕久  独立行政法人国立環境研究所, その他, 健康系領域長 (60281698)
Co-Investigator(Renkei-kenkyūsha) YAMANO Shigeru  福岡大学, 薬学部, 教授 (80140755)
TAKANO Hirohisa  独立行政法人国立環境研究所, 健康系領域長 (60281698)
Project Period (FY) 2006 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥15,910,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥2,610,000)
Fiscal Year 2008: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2007: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2006: ¥4,600,000 (Direct Cost: ¥4,600,000)
Keywords親電子性物質 / キノン系化合物 / 共有結合 / 大気汚染物質 / 多環芳香族炭化水素キノン類 / 大気汚染 / ナフタレン / ディーゼル排出微粒子 / ケミカルバイオロジー / チオールケミストリー
Research Abstract

本研究では大気汚染地域として知られている南カリフォルニア・リバーサイドで採取した大気中揮発性成分およびディーゼル排気曝露動物を用いて、タンパク質と共有結合する1, 2-ナフトキノンのような親電子性物質を認識する抗体の作成、本抗体の特異性、大気中揮発性成分に存在する親電子性物質とその分子標的について検討した。その結果、当該大気サンプル中には、1, 2-ナフトキノンとは異なる親電子性物質(群)が複数存在し、それらは細胞内レドックスセンサーであるPTP1Bに共有結合することで本酵素活性を低下させることが示唆された。

Report

(4 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (43 results)

All 2009 2008 2007 2006 Other

All Journal Article (25 results) (of which Peer Reviewed: 19 results) Presentation (15 results) Book (1 results) Remarks (2 results)

  • [Journal Article] The antioxidant defense system Keap1-Nrf2 comprises a multiple sensing mechanism for responding to a wide range chemical compounds.2009

    • Author(s)
      Kobayashi M
    • Journal Title

      Molecular and Cellular Biology 29

      Pages: 493-502

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Redox cycling of 9,10-phenanthraquinone to cause oxidative stress is terminated through its monoglucuronide conjugation in human pulmonary epithelial A549 cells2008

    • Author(s)
      Taguchi K, Shimada M, Fujii S,umi D, Pan XQ,Yamano S, Nishiyama T, Hiratsuka A, Yamamoto M, Cho AK, Froines JR, Kumagai Y
    • Journal Title

      Free Radical Biology & Medicine 2008 44

      Pages: 1945-1655

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] On the interaction between glyceraldehyde-3-phosphate dehydrogenase and airborne particles2008

    • Author(s)
      Shinyashiki M, Rodriguez CE, Di Stefano EW, Sioutas C, Delfino RJ, Kumagai Y, Froines JR, Cho AK
    • Journal Title

      Evidence for electrophilic species 42

      Pages: 517-529

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] A food-derived synergist of NGF signaling:Identification of protein tyrosine phosphatase 1B as a key regulator of NGF receptor-initiated signal transduction.2008

    • Author(s)
      Shibata T
    • Journal Title

      Journal of Neurochemistry 107

      Pages: 1248-1460

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Redox cycling of 9, 10-phenanthraquinone to cause oxidative stress is terminated through its monoglucuronide conjugation in human pulmonary epithelial A549 ce11s.2008

    • Author(s)
      Taguchi K
    • Journal Title

      Free Radical Biology & Medicine 44

      Pages: 1645-1655

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Xylulose, reductase is involved in 9, 10-phenanthrenequinone-induced apoptosis in human T lymphoma cells.2008

    • Author(s)
      Matsunaga T
    • Journal Title

      Free Radical Biology & Medicine 44

      Pages: 1191-1202

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] On theinteraction between glyceraldehyde-3-phosphatedehydrogenase and airborne particles:Evidence for electrophilic species.2008

    • Author(s)
      Shinyashiki M
    • Journal Title

      Atmospheric Environment 42

      Pages: 517-529

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Redox cycling of 9,10-phenanthraquinone to cause oxidative stress is terminated through its monoglucuronide conjugation in human pulmonary epithelial A549 cells.2008

    • Author(s)
      Taguchi K, et. al.
    • Journal Title

      Free Radical Biology & Medicine (in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Kalyanaraman, Hara A. Xylulose reductase is involved in 9,10-phenanthr enequinone-induced apoptosis in human T lymphoma cells2008

    • Author(s)
      Matsunaga T, et. al.
    • Journal Title

      Free Radical Biology & Medicine (in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] On the interaction between glyceraldehyde-3-phosphate dehydrogenase and airborne particles:Evidence for electrophilic species.2008

    • Author(s)
      Shinyashiki M, et. al.
    • Journal Title

      Archives of Toxicology 82

      Pages: 67-93

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chemical knockdown of protein tyrosine phosphatase 1B by 1, 2-naphthoquinone through covalent modification causes persistent transactivation of epidermal growth factor receptor2007

    • Author(s)
      Iwamoto N, Sumi D, Ishii T, Uchida K, Cho AK, Froines JR, Kumagai Y
    • Journal Title

      Journal of Biological Chemistry 2007 282

      Pages: 33396-33404

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] An approach to evaluate two-electron reduction of 9,10-phenanthraquinone and redox activity of the hydroquinone associated with oxidative stress2007

    • Author(s)
      Taguchi K, Fujii S, Yamano S, Cho AK, Kamisuki S, Nakai Y, Sugawara F, Froines JR, Kumagai Y
    • Journal Title

      Free Radical Biology & Medicine 2007 43

      Pages: 789-799

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effects of naphthoquinone on airway responsiveness in the presence or absence of antigen in mice2007

    • Author(s)
      Inoue KI, Takano H, Ichinose T, Tomura S, Yanagisawa R, Sakurai M, Sumi D, Hiyoshi K, Kumagai Y
    • Journal Title

      Archives of Toxicology 2007 81

      Pages: 575-581

    • NAID

      120007139196

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Naphthoquinone enhances antigen-related airway inflammation in mice2007

    • Author(s)
      Inoue KI, Takano H, Hiyoshi K, Ichinose T, Sadakane K, Yanagisawa R, Tomura S, Kumagai Y
    • Journal Title

      European Respiratory Journal 2007 29

      Pages: 259-267

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chemical knockdown of protein tyrosine phosphatase IB by 1,2-naphthoquinone through covalent modification causes persistent transactivation of epidermal growth factor receptor.2007

    • Author(s)
      Iwamoto N, et. al.
    • Journal Title

      Journal of Biological Chemistry 282

      Pages: 33396-33404

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 1,2-Naphthoquinone disrupts the function of cAMP response element-binding protein through covalent modification.2007

    • Author(s)
      Endo A, et. al.
    • Journal Title

      Biochemical and Biophysical Research Communications 361

      Pages: 243-248

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An approach to evaluate two-electron reduction of 9,10-phenanthraquinone and redox activity of the hydroquinone associated with oxidative stress.2007

    • Author(s)
      Taguchi K, et. al.
    • Journal Title

      Free Radical Biology & Medicine 43

      Pages: 789-799

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of naphthoquinone on airway responsiveness in the presence or absence of antigen in mice2007

    • Author(s)
      Inoue KI, et. al.
    • Journal Title

      Archives of Toxicology 81

      Pages: 575-581

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Naphthoquinone enhances antigen-related airway inflammation in mice.2007

    • Author(s)
      Inoue KI, et. al.
    • Journal Title

      European Respiratory Journal 29

      Pages: 259-267

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of naphthoquinone on airway responsiveness in the presence or absence of antigen in mice.2007

    • Author(s)
      Inoue KI, Takano H, Ichinose T, Tomura S, Yanagisawa R, Sakurai M, Sumi D, Hiyoshi K, Kumagai Y.
    • Journal Title

      Arch Toxicol. (In press)

    • NAID

      120007139196

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Naphthoquinone enhances antigen-related airway inflammation in mice.2007

    • Author(s)
      Inoue KI, Takano H, Hiyoshi K, Ichinose T, Sadakane K, Yanagisawa R, Tomura S, Kumagai Y.
    • Journal Title

      Eur Respir J. 29

      Pages: 259-267

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Arsenic : Signal Transduction, Transcription Factor, and Biotransformation Involved in Cellular Response and Toxicity.2007

    • Author(s)
      Kumagai Y, Sumi D.
    • Journal Title

      Annu Rev Pharmacol Toxicol. 47

      Pages: 243-262

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Sulforaphane, an activator of Nrf2, suppresses cellular accumulation of arsenic and its cytotoxicity in primary mouse hepatocytes.2006

    • Author(s)
      Shinkai Y, Sumi D, Fukami I, Ishii T, Kumagai Y.
    • Journal Title

      FEBS Letters. 580

      Pages: 1771-1774

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 1,2-Naphthoquinone activates vanilloid receptor 1 through increased protein tyrosine phosphorylation, leading to contraction of guinea pig trachea.2006

    • Author(s)
      Kikuno S, Taguchi K, Iwamoto N, Yamano S, Cho AK, Froines JR, Kumagai Y.
    • Journal Title

      Toxicology and Applied Pharmacology. 210

      Pages: 47-54

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Inhibition of Endothelial Nitric Oxide Synthase Activity and Suppression of Endothelium-Dependent Vasorelaxation by 1,2-Naphthoquinone, a Component of Diesel Exhaust Particles.2006

    • Author(s)
      Sun Y, Taguchi K, Sumi D, Yamano S, Kumagai Y.
    • Journal Title

      Arch Toxicol. 80

      Pages: 280-285

    • Related Report
      2006 Annual Research Report
  • [Presentation] 1,2-NQのCys121修飾によるプロテインチロシンホスファターゼ1B(PTP1B)の構造および活性への影響.2009

    • Author(s)
      岩本典子
    • Organizer
      第129年会日本薬学会
    • Place of Presentation
      京都
    • Year and Date
      2009-03-26
    • Related Report
      2008 Annual Research Report
  • [Presentation] 大気中に含まれる未知の親電子性物質とそれに対する生体応答を評価するシステムの構築2008

    • Author(s)
      西山彰、岩本典子、外山喬士、角大悟、熊谷嘉人
    • Organizer
      衛生薬学・環境トキシコロジー
    • Place of Presentation
      熊本
    • Year and Date
      2008-10-18
    • Related Report
      2008 Final Research Report
  • [Presentation] 1,2-ナフトキノンによるプロテインチロシンホスファタLーゼ1Bの活性阻害におけるCys121の役割.2008

    • Author(s)
      岩本典子
    • Organizer
      衛生薬学・環境トキシコロジー
    • Place of Presentation
      熊本
    • Year and Date
      2008-10-18
    • Related Report
      2008 Annual Research Report
  • [Presentation] 1,2-ナフトキノンはCys286を介して転写因子CREBに共有結合しその機能を阻害する.2008

    • Author(s)
      遠藤亜希子
    • Organizer
      衛生薬学・環境トキシコロジー
    • Place of Presentation
      熊本
    • Year and Date
      2008-10-18
    • Related Report
      2008 Annual Research Report
  • [Presentation] 大気中に含まれる未知の親電子性物質とそれにに対する生体応答を評価するシステムの構築.2008

    • Author(s)
      西山彰
    • Organizer
      衛生薬学・環壌トキシコロジー
    • Place of Presentation
      熊本
    • Year and Date
      2008-10-18
    • Related Report
      2008 Annual Research Report
  • [Presentation] 環境化学物質によるタンパク質の翻訳後修飾 : 毒性発現機構の解明に向けた修飾タンパク質の検出とその構造解析2008

    • Author(s)
      石井剛志、岩本典子、熊谷嘉人
    • Organizer
      第78回日本衛生学会総会
    • Place of Presentation
      熊本
    • Year and Date
      2008-03-29
    • Related Report
      2008 Final Research Report
  • [Presentation] Sticky pollutants: chemical knockdown of redox sensors.2007

    • Author(s)
      Kumagai Y, et. al.
    • Organizer
      The 2nd JST-ERATO Yamamoto Environmental Response Project International Symposium
    • Place of Presentation
      つくば
    • Year and Date
      2007-12-21
    • Related Report
      2007 Annual Research Report
  • [Presentation] 1, 2-ナフトキノンの解毒に関わるNrf2/Keap1システムの役割2007

    • Author(s)
      姜海燕、角大悟、田口恵子、Kit I. Tong、山本雅之、熊谷嘉人
    • Organizer
      衛生薬学・環境トキシコロジー
    • Place of Presentation
      大阪
    • Year and Date
      2007-11-02
    • Related Report
      2008 Final Research Report
  • [Presentation] 酸化ストレスを生じる1, 2-ナフトキノンの分子標的としてのチオレドキシン2007

    • Author(s)
      岩本典子、角大悟、石井剛志、内田浩二、中村肇、淀井淳司、熊谷嘉人
    • Organizer
      衛生薬学・環境トキシコロジー
    • Place of Presentation
      大阪
    • Year and Date
      2007-11-01
    • Related Report
      2008 Final Research Report
  • [Presentation] 酸化ストレスを生じる1,2-ナフトキノンの分子標的としてのチオレドキシン.2007

    • Author(s)
      岩本典子, 他
    • Organizer
      衛生薬学・環境トキシコロジー
    • Place of Presentation
      大阪
    • Year and Date
      2007-11-01
    • Related Report
      2007 Annual Research Report
  • [Presentation] 大気中親電子性物質によるPTP1B修飾に伴うEGFRリン酸化2007

    • Author(s)
      熊谷嘉人、岩本典子、角大悟
    • Organizer
      第7回分子予防環境医学研究会
    • Place of Presentation
      福岡
    • Year and Date
      2007-10-26
    • Related Report
      2008 Final Research Report
  • [Presentation] 大気中親電子性物質によるPTP1B修飾に伴うEGFRリン酸化.2007

    • Author(s)
      熊谷嘉人, 他
    • Organizer
      第7回分子予防環境医学研究会
    • Place of Presentation
      北九州
    • Year and Date
      2007-10-26
    • Related Report
      2007 Annual Research Report
  • [Presentation] 芳香族炭化水素キノン体によるPTF1Bの化学修飾とそれに伴うEGFRのリン酸化.2007

    • Author(s)
      熊谷嘉人, 他
    • Organizer
      北陸大学学術フロンティア・サテライトミーティング
    • Place of Presentation
      岐阜
    • Year and Date
      2007-07-27
    • Related Report
      2007 Annual Research Report
  • [Presentation] 大気中微小粒子成分によるERK1/2シグナル伝達経路の活性化2007

    • Author(s)
      岩本典子、張璧伊、角大悟、熊谷嘉人
    • Organizer
      第34回日本トキシコロジー学会 学術年会
    • Place of Presentation
      東京
    • Year and Date
      2007-06-27
    • Related Report
      2008 Final Research Report
  • [Presentation] 大気汚染物質のケミカルバイオロジー(その4) : ナフタレンの活性代謝物1, 2-ナフトキノンと共有結合する細胞内タンパク質を検出する免疫化学的方法2006

    • Author(s)
      三浦高、岩本典子、新開泰弘、角大悟、早川和一、熊谷嘉人
    • Organizer
      衛生薬学・環境トキシコロジー
    • Place of Presentation
      東京
    • Year and Date
      2006-10-30
    • Related Report
      2008 Final Research Report
  • [Book] YAKUGAKU ZASSHI2007

    • Author(s)
      Sumi D, et. al.
    • Total Pages
      7
    • Publisher
      日本薬学会
    • Related Report
      2007 Annual Research Report
  • [Remarks]

    • URL

      http://www.md.tsukuba.ac.jp/community-med/environmental_medicine/main/toppage.html

    • Related Report
      2008 Annual Research Report
  • [Remarks]

    • URL

      http://www.md.tsukuba.ac.jp/environmental_medicine/main/toppage.html

    • Related Report
      2007 Annual Research Report

URL: 

Published: 2006-04-01   Modified: 2016-04-21  

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