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Elucidation of HDL generation mechanism in hepatocytes

Research Project

Project/Area Number 15590952
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionNagoya City University

Principal Investigator

TSUJITA Maki  Nagoya City University, Graduate School of Medical Sciences, Research associates, 大学院・医学研究科, 助手 (10253262)

Co-Investigator(Kenkyū-buntansha) YOKOYAMA Shinji  Nagoya City University, Graduate School of Medical Sciences, Professor, 大学院・医学研究科, 教授 (10142192)
DOHMAE Sumiko  Nagoya City University, Graduate School of Medical Sciences, Assistant Professor, 大学院・医学研究科, 講師 (70227700)
OKAZAKI Mitsuyo  Tokyo Medical Dental University, College of Liberal Arts, Professor, 教養学部, 教授 (20013998)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsapolipoprotein AI / HDL generation / hepatocytes / monoclonal antibody / ABCA1 / Probucol / HepG2 cell / mouse primary hepatocytes / HDL / Hepatocyte / autocrine / 725-1E
Research Abstract

The mechanism for the assembly of HDL with cellular lipid by ABCA1 and helical apolipoprotein was investigated in hepatocytes. Both HepG2 cells and mouse primary culture hepatocytes produced HDL with apolipoprotein A-I whether endogenously synthesized or exogenously provided. Probucol, an ABCA1 inactivator, inhibited these reactions, as well as the reversible binding of apoAI to HepG2. Primary cultured hepatocytes of ABCA1-deficient mice also lacked HDL production regardless of the presenceof exogenous apoAI. HepG2 cells secreted apoAI into the medium even when ABCA1 was inactivated by probucol, but it was all in a free form as HDL production was inhibited. When a lipid-free apoAI-specific monoclonal antibody, 725-1E2, was present in the culture medium, production of HDL was suppressed, whether with endogenous or exogenously added apoAI, and the antibody did not influence HDL already produced by HepG2 cells. We concluded that the main mechanism for HDL assembly by endogenous apoAl in HepG2 cells is an autocrine-like reaction in which apoAI is secreted and then interacts with cellular ABCA1 to generate HDL.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (13 results)

All 2005 2004 2003

All Journal Article (13 results)

  • [Journal Article] On the hepatic mechanism of HDL assembly by the ABCA1/apoA-I pathway2005

    • Author(s)
      辻田麻紀, 呉成愛, 堂前純子, 臼井真一, 岡崎三代, 横山信治
    • Journal Title

      Journal of Lipid Reserach 46

      Pages: 154-162

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] On the hepatic mechanism of HDL assembly by the ABCA1/apoA-I pathway.2005

    • Author(s)
      Tsujita M, Wu CA, Abe-Dohmae S, Usui S, Okazaki M, Yokoyama S.
    • Journal Title

      J Lipid Res. 46(1)

      Pages: 154-162

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] An Inhibitor of acylCoA : cholesterol acyltransferase increases expression of ABC-binding cassett transporter AI and thereby enhances the ApoAI-mediated release of cholesterol from macrophages2004

    • Author(s)
      杉本佳奈美, 辻田麻紀, 呉成愛, 鈴木和夫, 横山信治
    • Journal Title

      Biochemica et Biophysica Acta 1636

      Pages: 69-76

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Potential involvement of dissociated apoA-I in the ABCA1-dependent cellular lipid release by HDL2004

    • Author(s)
      奥平桂一郎, 辻田麻紀, 山内祥生, 堂前純子, 加藤幸一, 半田哲夫, 横山信治
    • Journal Title

      Journal of Lipid Research 45

      Pages: 645-652

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Probucol Inactivates ABCA1 in the Plasma Membrane with Respect to Its Mediation of Apolipoprotein Binding and High Density Lipoprotein Assembly and to Its Proteolytic Degradation2004

    • Author(s)
      呉成愛, 辻田麻紀, 林弥智, 横山信治
    • Journal Title

      Journal of Biological Chemistry 279

      Pages: 30168-30174

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Isoosmotic Isolation of Rat Brain Synaptic Vesicles, Some of Which contain Tyrosine Hydroxylase2004

    • Author(s)
      都築紀宏, 辻田麻紀
    • Journal Title

      Journal of Biochemistry 136

      Pages: 239-243

    • NAID

      10016201609

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] An inhibitor of acylCoA: cholesterol acyltransferase increases expression of ATP-binding cassette transporter A1 and thereby enhances the ApoA-I-mediated release of cholesterol from macrophages.2004

    • Author(s)
      Sugimoto K, Tsujita M, Wu CA, Suzuki K, Yokoyama S.
    • Journal Title

      Biochim Biophys Acta. 1636(1)

      Pages: 69-76

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Potential involvement of dissociated apolipoprotein A-I in the ABCA1-dependent cellular lipid release by high density lipoprotein.2004

    • Author(s)
      Okuhira K, Tsujita M, Yamauchi Y, Abe-Dohmae S, Kato K, Handa T, Yokoyama S.
    • Journal Title

      J Lipid Res. 45(4)

      Pages: 645-652

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Probucol inactivates ABCA1 in the plasma membrane with respect to its mediation of apolipoprotein binding and high density lipoprotein assembly and to its proteolytic degradation.2004

    • Author(s)
      Wu CA, Tsujita M, Hayashi M, Yokoyama S.
    • Journal Title

      J Biol Chem. 279(29)

      Pages: 30168-30174

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Isoosmotic isolation of rat brain synaptic vesicles, some of which contain tyrosine hydroxylase.2004

    • Author(s)
      Tsudzuki T, Tsujita M.
    • Journal Title

      J Biochem (Tokyo). 136(2)

      Pages: 239-243

    • NAID

      10016201609

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 低HDL血症マウスにおけるストレス時の糖質コルチコイド産生抑制2003

    • Author(s)
      辻田麻紀, 呉成愛, 横山信治
    • Journal Title

      名古屋市立大医学会雑誌 54

      Pages: 155-165

    • NAID

      110007391179

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Stress-mediated corticosterone synthesis is defective in low plasma HDL mouse.2003

    • Author(s)
      Maki Tsujita, Cheng-ai Wu, Shinji Yokoyama
    • Journal Title

      Nagoyashiritudaigaku igakukaizasshi 54

      Pages: 155-165

    • NAID

      110007391179

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 低HDL血症マウスにおけるストレス時の糖質コルチコイド産生抑制2003

    • Author(s)
      辻田麻紀, 呉成愛, 横山信治
    • Journal Title

      名古屋市立大学医学会雑誌 54

      Pages: 155-165

    • NAID

      110007391179

    • Related Report
      2004 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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