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Analysis of role of transcription factor Nrf1 in protective response to heavy metals

Research Project

Project/Area Number 22790128
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Environmental pharmacy
Research InstitutionUniversity of Tsukuba

Principal Investigator

SHINKAI Yasuhiro  筑波大学, 医学医療系, 助教 (10454240)

Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2010: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords重金属 / カドミウム / メチル水銀 / Nrf1 / 血管内皮細胞 / 細胞応答システム / 抗酸化剤応答配列 / 生体防御システム
Research Abstract

Heavy metals such as cadmium and methylmercury are environmental pollutants that can target the vascular endothelium. In this study, we investigated the participation of transcription factor Nrf1 in cellular protective response to heavy metals. siRNA-mediated knockdown of Nrf1 resulted in an increase in sensitivity to cadmium and methylmercury in bovine aortic endothelial cells. Furthermore, exposure of cells to cadmium caused activation of Nrf1, leading to up-regulation of downstream genes such as NAD(P)H : quinone oxidereductase 1 and peroxiredoxin 1. Taken together, these results suggests that Nrf1 acts as a defense system against heavy metals. induced toxicity.

Report

(3 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • Research Products

    (49 results)

All 2012 2011 2010 Other

All Journal Article (19 results) (of which Peer Reviewed: 5 results) Presentation (27 results) Remarks (3 results)

  • [Journal Article] The chemical biology of naphthoquinones and its environmental implications2012

    • Author(s)
      Kumagai Y, Shinkai Y, Miura T, Cho AK
    • Journal Title

      Annual Review of Pharmacology and Toxicology

      Volume: 52 Pages: 221-247

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Journal Article] Detoxification of methylmercury by hydrogen sulfide producing enzyme in mammalian Cells2012

    • Author(s)
      Yoshida E, Toyama T, Shinkai Y, Sawa T, Akaike T, Kumagai Y
    • Journal Title

      Chemical Research in Toxicology

      Volume: 24 Pages: 1633-1635

    • Related Report
      2011 Final Research Report
  • [Journal Article] Peroxiredoxin 6 is a molecular target for1,2-naphthoquinone, an atmospheric electrophile2011

    • Author(s)
      Takayama N, Iwamoto N, Sumi D, Shinkai Y, Tanaka-Kagawa T, Jinno H, Kumagai Y
    • Journal Title

      in human pulmonary epithelial A549 cells. Journal of Toxicological Sciences

      Volume: 36 Pages: 817-821

    • Related Report
      2011 Final Research Report
  • [Journal Article] Glyceraldehyde-3-phosphatedehydrogenase as a quinone reductase in the suppression of 1,2-naphthoquinone protein adduct formation2011

    • Author(s)
      Miura T, Shinkai Y, Hirose R, Iwamoto N, Cho A K, Kumagai Y
    • Journal Title

      Free Radical Biology & Medicine

      Volume: 51 Pages: 2082-2089

    • Related Report
      2011 Final Research Report
  • [Journal Article] DNA microarray analysis of human neuroblastoma SH-SY5Y cells exposed to methylmercury2011

    • Author(s)
      Toyama T, Yoshida E, Shinkai Y, Kumagai Y
    • Journal Title

      Journal of Toxicological Sciences

      Volume: 36 Pages: 843-845

    • NAID

      10030037141

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Journal Article] GSH-mediated S-transarylation of a quinone glyceraldehyde-3-phosphatedehydrogenase conjugate2011

    • Author(s)
      Miura T, Kakehashi H, Shinkai Y, Egara Y, Hirose R, Cho AK, Kumagai Y
    • Journal Title

      Chemical Research in Toxicology

      Volume: 24 Pages: 1836-1844

    • Related Report
      2011 Final Research Report
  • [Journal Article] Participation of covalent modification of Keap1 in the activation of Nrf2 by tert-butylbenzoquinone, an electrophilic metabolite of butylated hydroxyanisole2011

    • Author(s)
      Abiko Y, Miura T, Bui H Phuc, Shinkai Y, Kumagai Y.
    • Journal Title

      Toxicology and Applied Pharmacology

      Volume: 255 Pages: 32-39

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Journal Article] Isothiocyanates reduce mercury accumulation via an Nrf2-dependent mechanism during exposure of mice to methylmercury2011

    • Author(s)
      Toyama T, Shinkai Y, Yasutake A, Uchida K, Yamamoto M, Kumagai Y.
    • Journal Title

      Environmental Health Perspective

      Volume: 119 Pages: 1117-1122

    • Related Report
      2011 Final Research Report
  • [Journal Article] Initial response and cellular protection through the Keap1/Nrf2 system during exposure of primary mouse hepatocytes to 1,2-naphthoquinone2011

    • Author(s)
      Miura T, Shinkai Y, Jiang HY, IwamotoN, Sumi D, Taguchi K, Yamamoto M, Jinno H, Tanaka-Kagawa T, Cho AK, Kumagai Y
    • Journal Title

      Chemical Research in Toxicology

      Volume: 24 Pages: 559-567

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Journal Article] Protective effect of pretreatment with cilostazol on cytotoxicity of cadmium and arsenite in cultured vascular endothelial cells2011

    • Author(s)
      Fujiwara Y, Banno H, Shinkai Y, Yamamoto C, Kaji T, Satoh M
    • Journal Title

      Journal of Toxicological Sciences

      Volume: 36 Pages: 155-161

    • NAID

      10028101091

    • Related Report
      2011 Final Research Report
  • [Journal Article] Detoxification of methylmercury by hydrogen sulfide-producing enzyme in Mammalian cells2011

    • Author(s)
      Yoshida E, Toyama T (equalcontributor), Shinkai Y, Sawa T, Akaike T, Kumagai Y
    • Journal Title

      Chemical Research in Toxicology

      Volume: 24 Issue: 10 Pages: 1633-1635

    • DOI

      10.1021/tx200394g

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Peroxiredoxin 6 is a molecular target for 1,2-naphthoquinone, an atmospheric electrophile, in human pulmonary epithelial A549 cells2011

    • Author(s)
      Takayama N
    • Journal Title

      The Journal of Toxicological Sciences

      Volume: 36 Issue: 6 Pages: 817-821

    • DOI

      10.2131/jts.36.817

    • NAID

      10030037072

    • ISSN
      0388-1350, 1880-3989
    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Glyceraldehyde-3-phosphate dehydrogenase as a quinone reductase in the suppression of 1,2-naphthoquinone protein adduct formation2011

    • Author(s)
      Miura T
    • Journal Title

      Free Radical Biology & Medicine

      Volume: 51 Issue: 11 Pages: 2082-2089

    • DOI

      10.1016/j.freeradbiomed.2011.09.008

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] GSH-mediated S-transarylation of a quinone glyceraldehyde-3-phosphate dehydrogenase conjugate2011

    • Author(s)
      Takashi Miura
    • Journal Title

      Chemical Research in Toxicology

      Volume: 24 Issue: 11 Pages: 1836-1844

    • DOI

      10.1021/tx200025y

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Isothiocyanates reduce mercury accumulation via an Nrf2-dependent mechanism during exposure of mice to methylmercury2011

    • Author(s)
      Toyama T, Shinkai Y, Yasutake A, Uchida K, Yamamoto M, Kumagai Y
    • Journal Title

      Environ Health Perspect

      Volume: 119 Issue: 8 Pages: 1117-1122

    • DOI

      10.1289/ehp.1003123

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Carbon monoxide derived from heme oxygenase-2 mediates reduction of methylmercury toxicity in SH-SY5Y cells2010

    • Author(s)
      Toyama T, Shinkai Y, Sumi D, Kumagai Y
    • Journal Title

      Toxicology and Applied Pharmacology

      Volume: 249 Pages: 86-90

    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Journal Article] Resistance of human brain microvascular endothelial cells in culture to methylmercury : cell-density-dependent defense mechanisms2010

    • Author(s)
      Hirooka T, Fujiwara Y, Shinkai Y, Yamamoto C, Yasutake A, Satoh M, EtoK, Kaji T
    • Journal Title

      Journal of Toxicological Sciences

      Volume: 35 Pages: 287-294

    • NAID

      10026469510

    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Journal Article] Signal transduction pathways and transcription factors triggered by arsenic trioxide in leukemia cells2010

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

      Toxicology and Applied Pharmacology

      Volume: 244 Pages: 385-392

    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Journal Article] Reduction of arsenic-induced cytotoxicity through Nrf2/HO-1 signaling in HepG2 cells2010

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

      Journal of Toxicological Sciences

      Volume: 35 Pages: 419-423

    • NAID

      10026469935

    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] 環境中親電子物質の細胞内運命2012

    • Author(s)
      新開泰弘
    • Organizer
      第28回臨床フリーラジカル会議
    • Place of Presentation
      京都府
    • Year and Date
      2012-01-20
    • Related Report
      2011 Final Research Report
  • [Presentation] 環境中親電子物質の細胞内運命2012

    • Author(s)
      新開泰弘
    • Organizer
      第28回臨床フリーラジカル会議
    • Place of Presentation
      京都
    • Year and Date
      2012-01-20
    • Related Report
      2011 Annual Research Report
  • [Presentation] カドミウムによる転写因子Nrf1の活性化とそれを介した細胞の適応機構2011

    • Author(s)
      新開泰弘, 伊藤友里, 山本千夏, 鍜冶利幸, 熊谷嘉人
    • Organizer
      メタロチオネインおよびメタルバイオサイエンス研究会2011
    • Place of Presentation
      愛知県
    • Year and Date
      2011-12-08
    • Related Report
      2011 Final Research Report
  • [Presentation] メチル水銀の解毒防御因子としての硫化水素2011

    • Author(s)
      吉田映子, 外山喬士, 新開泰弘, 熊谷嘉人
    • Organizer
      メタロチオネインおよびメタルバイオサイエンス研究会2011
    • Place of Presentation
      愛知県
    • Year and Date
      2011-12-08
    • Related Report
      2011 Final Research Report
  • [Presentation] ハイブリッド分子による血管内皮細胞のNrf2およびメタロチオネインの発現誘導2011

    • Author(s)
      藤江智也, 中寛史, 立浪忠志, 山本千夏, 廣岡孝志, 安池修之, 新開泰弘, 熊谷嘉人, 内山真伸, 鍜冶利幸
    • Organizer
      メタロチオネインおよびメタルバイオサイエンス研究会2011
    • Place of Presentation
      愛知県
    • Year and Date
      2011-12-08
    • Related Report
      2011 Final Research Report
  • [Presentation] カドミウムによる転写因子Nrf1の活性化とそれを介した細胞の適応機構2011

    • Author(s)
      新開泰弘
    • Organizer
      メタロチオネインおよびメタルバイオサイエンス研究会2011
    • Place of Presentation
      名古屋
    • Year and Date
      2011-12-08
    • Related Report
      2011 Annual Research Report
  • [Presentation] アクアポリン9はマウス初代肝細胞においてヒ素の細胞内蓄積とそれに伴う細胞毒性に関与する人2011

    • Author(s)
      新開泰弘, 角大悟, 外山喬士, 熊谷嘉人
    • Organizer
      第17回ヒ素シンポジウム
    • Place of Presentation
      茨城県
    • Year and Date
      2011-11-19
    • Related Report
      2011 Final Research Report
  • [Presentation] アクアポリン9はマウス初代肝細胞においてヒ素の細胞内蓄積とそれに伴う細胞毒性に関与する2011

    • Author(s)
      新開泰弘
    • Organizer
      第17回ヒ素シンポジウム
    • Place of Presentation
      つくば
    • Year and Date
      2011-11-19
    • Related Report
      2011 Annual Research Report
  • [Presentation] メチル水銀によるS-水銀化を介したソルビトール脱水素酵素の機能破綻2011

    • Author(s)
      外山喬士, 神田洋紀, 新開泰弘, 熊谷嘉人
    • Organizer
      衛生薬学・環境トキシコロジー
    • Place of Presentation
      石川県
    • Year and Date
      2011-10-28
    • Related Report
      2011 Final Research Report
  • [Presentation] 大気親電子物質1,4-ナフトキノンによるタンパク質の化学修飾を検出する免疫化学的手法の開発2011

    • Author(s)
      広瀬玲子, 三浦高, 新開泰弘, 香川(田中)聡子, 神野透人, 熊谷嘉人
    • Organizer
      衛生薬学・環境トキシコロジー
    • Place of Presentation
      石川県
    • Year and Date
      2011-10-28
    • Related Report
      2011 Final Research Report
  • [Presentation] グルタチオンの新 スな機能:大気中親電子物質による細胞内タンパク質の化学修飾制御に係わるS-トランスアリール化2011

    • Author(s)
      三浦高, 掛橋秀直, 新開泰弘, 熊谷嘉人
    • Organizer
      衛生薬学・環境トキシコロジー
    • Place of Presentation
      石川県
    • Year and Date
      2011-10-27
    • Related Report
      2011 Final Research Report
  • [Presentation] カドミウムによる親電子物質応答配列を介した転写因子Nrf1 の活性化2011

    • Author(s)
      伊藤友里, 新開泰弘, 山本千夏, 鍜冶利幸, 熊谷嘉人
    • Organizer
      衛生薬学・環境トキシコロジー
    • Place of Presentation
      石川県
    • Year and Date
      2011-10-27
    • Related Report
      2011 Final Research Report
  • [Presentation] ブチルヒドロキシアニソールで生じるNrf2 活性化はその親電子代謝物によるKeap1 の化学修飾が関与する2011

    • Author(s)
      安孫子ユミ, 岩本典子, Bui Hoang Phuc, 新開泰弘, 熊谷嘉人
    • Organizer
      第38回日本トキシコロジー学会学術集会
    • Place of Presentation
      神奈川県
    • Year and Date
      2011-07-11
    • Related Report
      2011 Final Research Report
  • [Presentation] The Keap1-Nrf2 system regulates metallothionein expression and protects vascular endothelial cells from cadmium cytotoxicity2011

    • Author(s)
      Shinkai Y, Kumagai Y, Kimura T,Yamamoto C, Yamamoto M, Jinno H,Tanaka-Kagawa T, Kaji T
    • Organizer
      Society of Toxicology 50th Annual Meeting
    • Place of Presentation
      Washington DC, USA
    • Year and Date
      2011-03-08
    • Related Report
      2011 Final Research Report
  • [Presentation] Mechanisms bywhich glyceraldehyde-3-phosphatedehydrogenase protects itself against achemical modification2011

    • Author(s)
      Miura T, Egara Y, Hirose R, Iwamoto N, Shinkai Y, Jinno H, Tanaka-Kagawa T, Cho AK, Kumagai Y
    • Organizer
      Society of Toxicology 50th Annual Meeting
    • Place of Presentation
      Washington DC, USA
    • Year and Date
      2011-03-08
    • Related Report
      2011 Final Research Report
  • [Presentation] HepG2細胞においてNrf2/HO-1シグナルの活性化はヒ素の毒性の軽減に関与する2011

    • Author(s)
      安孫子ユミ、新開泰弘、角大悟、熊谷嘉人
    • Organizer
      第16回ヒ素シンポジウム
    • Place of Presentation
      北海道
    • Year and Date
      2011-02-05
    • Related Report
      2011 Final Research Report
  • [Presentation] Keap1/Nrf2システムを介したメチル水銀に対する生体応答・毒性防御2011

    • Author(s)
      熊谷嘉人、外山喬士、新開泰弘、角大悟、山本雅之
    • Organizer
      第10回分子予防環境医学研究会
    • Place of Presentation
      京都府
    • Year and Date
      2011-01-21
    • Related Report
      2011 Final Research Report
  • [Presentation] ブチルヒドロキシアニソールの親電子代謝物によるKeap1/Nrf2システムの活性化2010

    • Author(s)
      安孫子ユミ,Bui Hoang Phuc,岩本典子,新開泰弘,熊谷嘉人
    • Organizer
      衛生薬学・環境トキシコロジー
    • Place of Presentation
      東京都
    • Year and Date
      2010-09-10
    • Related Report
      2011 Final Research Report
  • [Presentation] S-トランスアルキル化を介した親電子修飾の自己制御タンパク質の同定2010

    • Author(s)
      矢澤亜季、岩本典子、安孫子ユミ、浅井聡、三浦高、新開泰弘、熊谷嘉人
    • Organizer
      衛生薬学・環境トキシコロジー
    • Place of Presentation
      東京都
    • Year and Date
      2010-09-10
    • Related Report
      2011 Final Research Report
  • [Presentation] 血管内皮細胞において鉛はJNK-AP-1経路を介して小胞体シャペロンGRP78およびGRP94 を誘導する2010

    • Author(s)
      新開泰弘、山本千夏、鍜冶利幸、熊谷嘉人
    • Organizer
      衛生薬学・環境トキシコロジー
    • Place of Presentation
      東京都
    • Year and Date
      2010-09-10
    • Related Report
      2011 Final Research Report
  • [Presentation] 親電子修飾の自己制御能を有する解糖系酵素としてのグリセルアルデヒド3-リン酸脱水素酵素2010

    • Author(s)
      三浦高、岩本典子、新開泰弘、熊谷嘉人
    • Organizer
      衛生薬学・環境トキシコロジー
    • Place of Presentation
      東京都
    • Year and Date
      2010-09-09
    • Related Report
      2011 Final Research Report
  • [Presentation] 血管内皮細胞において鉛はJNK-AP-1経路を介して小胞体シャペロンGRP78およびGRP94を誘導する2010

    • Author(s)
      新開泰弘
    • Organizer
      フォーラム2010:衛生薬学・環境トキシコロジー
    • Place of Presentation
      東京
    • Year and Date
      2010-09-09
    • Related Report
      2010 Annual Research Report
  • [Presentation] Nrf2-dependent protection against methylmercury toxicity in vitro and in vivo2010

    • Author(s)
      Kumagai Y, Toyama T, Shinkai Y, Yasutake A
    • Organizer
      XII International Congress of Toxicology
    • Place of Presentation
      Balcelona, Spain
    • Year and Date
      2010-07-22
    • Related Report
      2011 Final Research Report
  • [Presentation] 血管内皮細胞においてNrf1はカドミウムに対する防御応答を担う転写因子である2010

    • Author(s)
      新開泰弘
    • Organizer
      第37回日本トキシコロジー学会学術年会
    • Place of Presentation
      沖縄
    • Year and Date
      2010-06-18
    • Related Report
      2010 Annual Research Report
  • [Presentation] 血管内皮細胞においてNrf1はカドミウムに対する防御応答を担う転写因子である2010

    • Author(s)
      新開泰弘、山本千夏、鍛治利幸、熊谷嘉人
    • Organizer
      第37回日本トキシコロジー学会学術年会
    • Place of Presentation
      沖縄県
    • Year and Date
      2010-06-17
    • Related Report
      2011 Final Research Report
  • [Presentation] メチル水銀の解毒排泄における転写因子Nrf2の役割2010

    • Author(s)
      新開泰弘、外山喬士、安武章、山本雅之、熊谷嘉人
    • Organizer
      第80回日本衛生学会学術総会
    • Place of Presentation
      宮城県
    • Year and Date
      2010-05-11
    • Related Report
      2011 Final Research Report
  • [Presentation] メチル水銀の解毒排泄における転写因子Nrf2の役割2010

    • Author(s)
      新開泰弘
    • Organizer
      第80回日本衛生学会学術総会
    • Place of Presentation
      仙台
    • Year and Date
      2010-05-10
    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.md.tsukuba.ac.jp/environmental_medicine/index.html

    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.md.tsukuba.ac.jp/environmental_medicine/index.html

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

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

    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2016-04-21  

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