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Exploration of a novel role for lidocaine as a wide range spectrum anti-infection drug

Research Project

Project/Area Number 22591112
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Infectious disease medicine
Research InstitutionTokyo Women's Medical University

Principal Investigator

TAKAKUWA Yuichi  東京女子医科大学, 医学部, 教授 (40113740)

Co-Investigator(Kenkyū-buntansha) KOSHINO Ichiro  東京女子医科大学, 医学部, 助教 (80328377)
MANNO Sumie  東京女子医科大学, 医学部, 講師 (10101205)
TANAKA Shotaro  東京女子医科大学, 医学部, 助教 (90380667)
ARASHIKI Nobuto  東京女子医科大学, 医学部, 助教 (80569658)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywords脂質ラフト / リドカイン / Plasmodium falciparum / Feline immunodeficiency virus / 抗感染症薬 / 感染症 / シグナル伝達 / G蛋白質共役受容体
Research Abstract

Plasmodium falciparum, a causative agent of malaria, and feline immunodeficiency virus were used as models for parasitic and viral infection, respectively. Lidocaine treatment disrupted lipid rafts in respective host cells and concomitantly inhibited the parasite invasion and viral entry. Detailed study revealed that malaria parasites activateraft-mediated signal transduction in host erythrocytes to phosphorylate dematin, a membrane skeletal protein. Phosphorylation of dematin results in a transient loosening of membrane skeletal meshwork, allowing the parasite invasion. Lidocain was shown to inhibit the parasite invasion by preventing membrane skeletal loosening via disruption of lipid rafts

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (25 results)

All 2013 2012 2011 2010 Other

All Journal Article (2 results) (of which Peer Reviewed: 1 results) Presentation (23 results) (of which Invited: 1 results)

  • [Journal Article] Identification of a novel role for dematin in regulating red cell membrane function by modulating spectrin-actin interaction2012

    • Author(s)
      Koshino, I., Mohandas, N., andTakakuwa, Y.
    • Journal Title

      J. Biol. Chem

      Volume: 287 Pages: 35244-35250

    • Related Report
      2012 Final Research Report
  • [Journal Article] Identification of a novel role for dematin in regulating red cell membrane function by modulating spectrin-actin interaction.2012

    • Author(s)
      Ichiro Koshino
    • Journal Title

      J. Biol. Chem.

      Volume: 287 Issue: 42 Pages: 35244-35250

    • DOI

      10.1074/jbc.m111.305441

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] 生体膜の本質に迫る2013

    • Author(s)
      高桑 雄一
    • Organizer
      日本膜学会第35年会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 局所麻酔薬リドカインによる抗ウイルス効果の検討2013

    • Author(s)
      越野 一朗
    • Organizer
      日本膜学会第35年会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
  • [Presentation] Possible involvement of ATP derived from infected erythrocytes in invasion by Plasmodium falciparum2012

    • Author(s)
      越野 一朗
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
  • [Presentation] マラリア原虫の赤血球侵入に利用されるGPCRアゴニストに関する検討2012

    • Author(s)
      越野 一朗
    • Organizer
      日本膜学会第34年会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
  • [Presentation] Identification of a novel role for dematin in regulating red cell membrane mechanical function by PKA phosphorylation-dependent modulation of spectrin-actin interaction2011

    • Author(s)
      Ichiro Koshino, Narla Mohandas, Yuichi Takakuwa
    • Organizer
      Red Cell Club Meeting 2011
    • Place of Presentation
      Philadelphia, USA
    • Year and Date
      2011-10-14
    • Related Report
      2011 Annual Research Report
  • [Presentation] Identification of the GPCR-agonist utilized by Plasmodium falciparum2011

    • Author(s)
      越野一朗、高桑雄一
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都
    • Year and Date
      2011-09-24
    • Related Report
      2011 Annual Research Report
  • [Presentation] Erythrocyte raft-dependent signal transduction pathway involved in Plasmodium falciparum invasion of erythrocytes2011

    • Author(s)
      Ichiro Koshino, Yuichi Takakuwa
    • Organizer
      International Union of Microbiological Societies Congress 2011
    • Place of Presentation
      Sapporo
    • Year and Date
      2011-09-09
    • Related Report
      2011 Annual Research Report
  • [Presentation] マラリア原虫が赤血球侵入時に利用する情報伝達経路の解明2011

    • Author(s)
      越野一朗、高桑雄一
    • Organizer
      日本膜学会第33年会
    • Place of Presentation
      東京
    • Year and Date
      2011-05-12
    • Related Report
      2011 Annual Research Report
  • [Presentation] Clever mechanism for malaria parasite invasion of human erythrocytes : innocent participation of the erythrocyte raft-dependent signal transduction pathway2010

    • Author(s)
      越野一朗、高桑雄一
    • Organizer
      3^<rd>. Indo-Japanese International Joint Symposium on Overcoming Intractable Infectious Diseases Prevalent in Asian Countries
    • Place of Presentation
      東京理科大学 森戸記念館(東京都)
    • Year and Date
      2010-12-14
    • Related Report
      2010 Annual Research Report
  • [Presentation] マラリア原虫の侵入における赤血球膜骨格蛋白質デマチンの役割2010

    • Author(s)
      越野一朗、高桑雄一
    • Organizer
      第83回日本生化学会大会
    • Place of Presentation
      神戸ポートアイランド(兵庫県)
    • Year and Date
      2010-12-08
    • Related Report
      2010 Annual Research Report
  • [Presentation] デマチンのPKAリン酸化による赤血球膜骨格機能の調節2010

    • Author(s)
      越野一朗、高桑雄一
    • Organizer
      日本膜学会第32年会
    • Place of Presentation
      産総研臨海副都心センター(東京都)
    • Year and Date
      2010-05-14
    • Related Report
      2010 Annual Research Report
  • [Presentation] 局所麻酔薬リドカインによる抗ウイルス効果の検討

    • Author(s)
      越野一朗、 高桑雄一
    • Organizer
      日本膜学会第35 年会
    • Related Report
      2012 Final Research Report
  • [Presentation] Possibleinvolvement of ATP derived from infected erythrocytes in invasion by Plasmodium falciparum

    • Author(s)
      野 一 朗 、 高 桑 雄 一
    • Organizer
      第85回日本生化学会大会
    • Related Report
      2012 Final Research Report
  • [Presentation] マラリア原虫の赤血球侵入に利用される GPCR アゴニストに関する検討

    • Author(s)
      越野一朗、 高桑雄一
    • Organizer
      日本膜学会第34 年会
    • Related Report
      2012 Final Research Report
  • [Presentation] Identification of the GPCR-agonist utilized by P. falciparum

    • Author(s)
      越野一朗、 高桑雄一
    • Organizer
      第84回日本生化学会大会
    • Related Report
      2012 Final Research Report
  • [Presentation] Identification of a novel role for dematin in regulating red cell membrane mechanical function by PKA phosphorylation-dependent modulation of spectrin-actin interaction

    • Author(s)
      Koshino, I, Mohandas, N., and Takakuwa Y
    • Organizer
      Red Cell Club Annual Meeting 2011
    • Related Report
      2012 Final Research Report
  • [Presentation] Erythrocyte raft-dependent signal transduction pathway involved in Plasmodium falciparum invasion of erythrocytes

    • Author(s)
      Koshino, I. and Takakuwa, Y
    • Organizer
      International Union of Microbiological Societies Congress 2011
    • Related Report
      2012 Final Research Report
  • [Presentation] マラリア原虫が赤血球侵入に利用する情報伝達経路の解明

    • Author(s)
      越野一朗、 高桑雄一
    • Organizer
      日本膜学会第33 年会
    • Related Report
      2012 Final Research Report
  • [Presentation] lever Mechanism for malaria parasite invasion of human erythrocytes: Innocent participation of the erythrocyte raft-dependent signal transduction pathway

    • Author(s)
      Koshino, I. and Takakuwa, Y.
    • Organizer
      3rd Indo-Japanese Infectious Disease Symposium
    • Related Report
      2012 Final Research Report
  • [Presentation] マラリア原虫の侵入における赤血球膜骨格蛋白質デマチンの役割

    • Author(s)
      越野一朗、 高桑雄一
    • Organizer
      第83回日本生化学会大会
    • Related Report
      2012 Final Research Report
  • [Presentation] 脂質ラフトを舞台とした熱帯熱マラリア原虫の赤血球侵入機構とその防御

    • Author(s)
      高桑雄一
    • Organizer
      日本血液学会
    • Related Report
      2012 Final Research Report
  • [Presentation] デマチンの PKAリン酸化による赤血球膜骨格機能の調節

    • Author(s)
      越野一朗、高桑雄一
    • Organizer
      日本膜学会第32 年会
    • Related Report
      2012 Final Research Report
  • [Presentation] Regulation of erythrocyte membrane stability and malaria parasite invasion by lipid raft-dependent signal transduction

    • Author(s)
      Koshino, I. and Takakuwa, Y.
    • Organizer
      The 13th International Membrane Research Forum, The 6^(th) iCeMS International Symposium
    • Related Report
      2012 Final Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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