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2010 Fiscal Year Final Research Report

Development of HDL-raising drugs targeting ABCA1

Research Project

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Project/Area Number 21790739
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Circulatory organs internal medicine
Research InstitutionNagoya City University

Principal Investigator

IWAMOTO Noriyuki  Nagoya City University, 大学院・医学研究科, 研究員 (70534709)

Project Period (FY) 2009 – 2010
KeywordsABCA1 / コレステロール / HDL / PKC / AP2 / カルモジュリン / カルパイン / アポリポプロテイン
Research Abstract

ABCA1 expression is regulated negatively by a transcriptional factor AP2 and its protein level is modulated by calpain-mediated proteolytic degradation. In this research project, I demonstrated that regulation of the ABCA1 gene by AP2 is mediated by its phosphorylation by PKD, which is similar to negative regulation of the adiponectin gene. I also showed that calmodulin binds ABCA1 and suppress its calpain-mediated degradation. A calmodulin inhibitor W7 enhanced calmodulin binding to ABCA1 to increase HDL biogenesis.

  • Research Products

    (7 results)

All 2011 2010 2009

All Journal Article (3 results) (of which Peer Reviewed: 3 results) Presentation (4 results)

  • [Journal Article] Protein kinase D regulates the adiponectin gene expression through phosphorylation of AP-2 ; a common pathway to the ABCA1 gene regulation.2011

    • Author(s)
      Noriyuki Iwamoto, Shinji Yokoyama.
    • Journal Title

      Atherosclr. 216

      Pages: 90-96

    • Peer Reviewed
  • [Journal Article] Calmodulin Interacts with ATP Binding Cassette Transporter A1 to Protect from Calpain-Mediated Degradation and Upregulates High Density Lipoprotein Generation.2010

    • Author(s)
      Noriyuki Iwamoto, Rui Lu, Nobukiyo Tanaka, Sumiko Abe-dohmae, Shinji Yokoyama
    • Journal Title

      Arterioscler. Thromb.Vasc.Biol. 30

      Pages: 1446-1452

    • Peer Reviewed
  • [Journal Article] Helical Apolipoproteins of High-Density Lipoprotein Enhance Phagocytosis by Stabilizing ATP-Binding Cassette Transporter A7.2010

    • Author(s)
      Nobukiyo Tanaka, Sumiko Abe-Dohmae, Noriyuki Iwamoto, Michael L.Fitzgerald, Shinji Yokoyama.
    • Journal Title

      J.Lipid Res. 51

      Pages: 2591-2599

    • Peer Reviewed
  • [Presentation] FHにおける妊娠とLDLアフェレシス2010

    • Author(s)
      岩本紀之
    • Organizer
      日本アフェレシス学会
    • Place of Presentation
      東京
    • Year and Date
      2010-11-04
  • [Presentation] Regulation of ATP-Binding Cassette (ABC) tyansporter in Sterol Metabokism2010

    • Author(s)
      岩本紀之
    • Organizer
      日本動脈硬化学会
    • Place of Presentation
      岐阜
    • Year and Date
      2010-07-15
  • [Presentation] 転写調節因子AP2αによる細胞内脂質排出に関わる遺伝子調節機構2009

    • Author(s)
      岩本紀之
    • Organizer
      日本脂質生化学会
    • Place of Presentation
      名古屋
    • Year and Date
      2009-07-30
  • [Presentation] Calmodulin interacts with ABCA1 and regulate its expression level.2009

    • Author(s)
      岩本紀之
    • Organizer
      日本動脈硬化学会
    • Place of Presentation
      山口
    • Year and Date
      2009-07-17

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Published: 2012-02-13   Modified: 2016-04-21  

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