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Mechanisms underlying endothelial metallothionein induction based on the strategy of bioorganometallics

Research Project

Project/Area Number 15K14992
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Environmental and hygienic pharmacy
Research InstitutionTokyo University of Science

Principal Investigator

Kaji Toshiyuki  東京理科大学, 薬学部薬学科, 教授 (90204388)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsバイオオルガノメタリクス / メタロチオネイン / 有機-無機ハイブリッド分子 / 誘導 / 血管内皮細胞 / 有機-無機ハイブリッド分子
Outline of Final Research Achievements

The present study revealed that induction of metallothionein (MT) isoforms MT-1 and MT-2 of vascular endothelial cells mediated by the MTF-1-MRE pathway and Nrf2-ARE pathway, respectively, using organic-inorganic hybrid molecules. Additionally, it was also revealed that induction of MT-1A and MT-2A is mediated by the ALK5-Smad2/Smad4-Sp1 pathway and ALK5-Smad2-Sp1pathway, respectively. It has been postulated that there is no functional difference between MT-1 and MT-2, however, the present results suggest the functional differentiation between the MT isoforms.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (23 results)

All 2018 2017 2016 2015 Other

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 7 results,  Acknowledgement Compliant: 4 results) Presentation (15 results) (of which Invited: 6 results) Remarks (1 results)

  • [Journal Article] Copper diethyldithiocarbamate as an inhibitor of tissue plasminogen activator synthesis in cultured human coronary endothelial cells2017

    • Author(s)
      Fujie Tomoya、Okino Shiori、Yoshida Eiko、Yamamoto Chika、Naka Hiroshi、Kaji Toshiyuki
    • Journal Title

      The Journal of Toxicological Sciences

      Volume: 42 Issue: 5 Pages: 553-558

    • DOI

      10.2131/jts.42.553

    • NAID

      130006076730

    • ISSN
      0388-1350, 1880-3989
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transcriptional induction of metallothionein by tris(pentafluorophenyl)stibane in cultured bovine aortic endothelial cells2016

    • Author(s)
      Fujie, T., Murakami, M., Yoshida, E., Yasuike, S., Kimura, T., Fujiwara, Y., Yamamoto, C. and Kaji, T.
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 17 Issue: 9 Pages: 1381-1381

    • DOI

      10.3390/ijms17091381

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Toxicology of organic-inorganic hybrid molecules: bio-organometallics and its toxicology2016

    • Author(s)
      Fujie, T., Hara, T. and Kaji, T.
    • Journal Title

      The Journal of Toxicological Sciences

      Volume: 41 Issue: Special Pages: SP81-SP88

    • DOI

      10.2131/jts.41.SP81

    • NAID

      130005450523

    • ISSN
      0388-1350, 1880-3989
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Induction of metallothionein isoforms by copper diethyldithiocarbamate in cultured vascular endothelial cells2016

    • Author(s)
      Fujie T, Segawa Y, Yoshida E, Kimura T, Fujiwara Y, Yamamoto C, Satoh M, Naka H, Kaji T.
    • Journal Title

      The Journal of Toxicological Sciences

      Volume: 41 Issue: 2 Pages: 225-232

    • DOI

      10.2131/jts.41.225

    • NAID

      130005132663

    • ISSN
      0388-1350, 1880-3989
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Zinc diethyldithiocarbamate as an inducer of metallothionein in cultured vascular endothelial cells2016

    • Author(s)
      Fujie T, Segawa Y, Uehara A, Nakamura T, Kimura T, Yoshida E, Yamamoto C, Uchiyama M, Naka H, Kaji T.
    • Journal Title

      The Journal of Toxicological Sciences

      Volume: 41 Issue: 2 Pages: 217-224

    • DOI

      10.2131/jts.41.217

    • NAID

      130005132664

    • ISSN
      0388-1350, 1880-3989
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Copper diethyldithiocarbamate as an activator of Nrf2 in cultured vascular endothelial cells.2016

    • Author(s)
      Fujie T, Murakami M, Yoshida E, Tachinami T, Shinkai Y, Fujiwara Y, Yamamoto C, Kumagai Y, Naka H, Kaji T.
    • Journal Title

      Journal of Biological Inorganic Chemistry

      Volume: 21 Issue: 2 Pages: 263-273

    • DOI

      10.1007/s00775-016-1337-z

    • NAID

      120007135582

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Partial contribution of the Keap1-Nrf2 system to cadmium-mediated metallothionein expression in vascular endothelial cells.2016

    • Author(s)
      Shinkai Y, Kimura T, Itagaki A, Yamamoto C, Taguchi K, Yamamoto M, Kumagai Y, Kaji T.
    • Journal Title

      Toxicol Appl Pharmacol

      Volume: 295 Pages: 37-46

    • DOI

      10.1016/j.taap.2016.01.020

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 有機-無機ハイブリッド分子を活用した血管内皮細胞のメタロチオネイン転写誘導機構の解析2018

    • Author(s)
      竹中 福太,吉田 映子,藤江 智也,山本 千夏,安池 修之,鍜冶 利幸
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 有機-無機ハイブリッド分子の血管毒性学2017

    • Author(s)
      鍜冶 利幸
    • Organizer
      プラズマ分光分析研究会第99回講演会
    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Invited
  • [Presentation] 重金属の細胞毒性に対する血管内皮細胞の防御系2017

    • Author(s)
      藤江 智也,山本 千夏,鍜冶 利幸
    • Organizer
      第44回日本毒性学会学術年会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] ジチオカルバメート錯体による血管内皮および平滑筋細胞のメタロチオネイン発現の誘導2017

    • Author(s)
      藤江 智也,土田 あずさ,中 寛史,鍜冶 利幸,山本 千夏
    • Organizer
      第44回日本毒性学会学術年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 銅錯体による血管平滑筋細胞のメタロチオネイン発現の誘導2017

    • Author(s)
      藤江 智也,二宮 早紀,中 寛史,鍜冶 利幸,山本 千夏
    • Organizer
      第44回日本毒性学会学術年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] バイオオルガノメタリクス:重金属毒性学から生まれた新しい研究戦略2017

    • Author(s)
      鍜冶 利幸
    • Organizer
      国際科学技術共同研究推進事業 戦略的国際共同研究プログラム:日本ー中国共同研究 都市における環境問題または都市におけるエネルギー問題に関する研究分野
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] TGF- βシグナルを介した血管内皮細胞メタロチオネインの誘導2017

    • Author(s)
      土田 翼,藤江 智也,吉田 映子,藤原 泰之,山本 千夏,鍜冶 利幸
    • Organizer
      フォーラム2017 衛生薬学・環境トキシコロジー
    • Related Report
      2017 Annual Research Report
  • [Presentation] ジチオカルバメート錯体による血管内皮細胞選択的なメタロチオネイン発現の誘導2017

    • Author(s)
      藤江 智也,土田 あずさ,中 寛史,鍜冶 利幸,山本 千夏
    • Organizer
      フォーラム2017 衛生薬学・環境トキシコロジー
    • Related Report
      2017 Annual Research Report
  • [Presentation] バイオオルガノメタリクスの到達点と課題2017

    • Author(s)
      鍜冶 利幸
    • Organizer
      東京理科大学総合研究院バイオオルガノメタリクス研究部門研究交流会
    • Place of Presentation
      東京理科大学神楽坂校舎2号館(東京都新宿区)
    • Related Report
      2016 Research-status Report
  • [Presentation] 銅錯体による血管内皮細胞メタロチオネイン誘導を介在する亜鉛輸送体ZIP7の発現誘導2016

    • Author(s)
      藤江 智也,森田 遥香,吉田 映子,藤原 泰之,山本 千夏,中 寛史,鍜冶 利幸
    • Organizer
      日本毒性学会第43回学術年会
    • Place of Presentation
      愛知県産業労働センター(愛知県名古屋市)
    • Year and Date
      2016-06-29
    • Related Report
      2016 Research-status Report
  • [Presentation] 重金属の血管毒性研究からバイオ元素戦略バイオオルガノメタリクスへ2015

    • Author(s)
      鍜冶利幸
    • Organizer
      第604回新潟薬科大学薬学総合セミナー
    • Place of Presentation
      新潟薬科大学(新潟県新潟市)
    • Year and Date
      2015-11-27
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 銅錯体による血管内皮細胞メタロチオネイン誘導を制御する亜鉛輸送体 ZIP72015

    • Author(s)
      森田 遥香,藤江 智也,中 寛史,吉田 映子,鍜冶 利幸
    • Organizer
      フォーラム2015 衛生薬学・環境トキシコロジー
    • Place of Presentation
      神戸学院大学(兵庫県神戸市)
    • Year and Date
      2015-09-17
    • Related Report
      2015 Research-status Report
  • [Presentation] 有機-無機ハイブリッド分子を活用した血管内皮細胞メタロチオネイン誘導機構の解析2015

    • Author(s)
      藤江 智也,鍜冶 利幸
    • Organizer
      第2回東京環境健康薬学研究会
    • Place of Presentation
      東京理科大学(東京都新宿区神楽坂)
    • Year and Date
      2015-08-21
    • Related Report
      2015 Research-status Report
  • [Presentation] 有機金属化合物の細胞毒性2015

    • Author(s)
      山本 千夏,安池 修之,鍜冶 利幸
    • Organizer
      第42回日本毒性学会学術年会
    • Place of Presentation
      ホテル日航金沢(石川県金沢市)
    • Year and Date
      2015-06-29
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 有機-無機ハイブリッド分子を活用した血管内皮細胞のメタロチオネイン誘導機構の解明2015

    • Author(s)
      鍜冶 利幸
    • Organizer
      第42回日本毒性学会学術年会
    • Place of Presentation
      金沢市アートホール(石川県金沢市)
    • Year and Date
      2015-06-29
    • Related Report
      2015 Research-status Report
    • Invited
  • [Remarks] 東京理科大学薬学部環境健康学教室(鍜冶研究室)

    • URL

      http://www.rs.tus.ac.jp/kaji-lab/

    • Related Report
      2017 Annual Research Report 2016 Research-status Report 2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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