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Enhancement of cellular cholesterol efflux and atherosclerosis treatwent by pharmacological stimulation of an apolipoprotein receptor(s)

Research Project

Project/Area Number 09557081
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field 内分泌・代謝学
Research InstitutionNagoya City University

Principal Investigator

YOKOYAMA Sinji  Nagoya City University, Medical School, professor, 医学部, 教授 (10142192)

Co-Investigator(Kenkyū-buntansha) TSUJITA Maki  Nagoya City University, Medical School, research associate, 医学部, 助手 (10253262)
ABE-DOHMAE Sumiko  Nagoya City University, Medical School, assistant professor, 医学部, 講師 (70227700)
ITO Jinichi  Nagoya City University, Medical School, assistant professor, 医学部, 講師 (60167260)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1998: ¥4,500,000 (Direct Cost: ¥4,500,000)
KeywordsCholesterol / HDL / Apolipoprotein / Cell / Signal Transduction / 動脈硬化
Research Abstract

Two independent mechanisms are known for cellular cholesterol removal ; physicochemical diffusion and apolipoprotein-cell interaction that causes HDL neogenesis. This research project focused on the latter pathway to achieve the results as follows. 1) Mouse monocytic leukemia cell line cells RAW264 require cAMP for apolipoprotein-mediated HDL generation, and naphthalene sulfonamides known as calmodulin inhibitors enhanced the HDL generation in this condition. This effect was unique to these compounds, being not shared with other calmodulin inhibitors. 2) In vivo regulation of plasma HDL level by the apolipoprotein-mediated HDL generation was studied by using the mice fed with probucol that inhibits the cell/apolipoprotein interaction. Probucol remarkably reduces the HDL level within 2 weeks without changing apoA-I biosynthesis and the plasma HDL clearance rate. Peritoneal macrophages obtained from these animals lost the apoA-I binding, HDL generation and the reactive intracellular cholesterol trafficking. Therefore, reduction of HDL cholesterol was shown to be due to the lack of apolipoprotein/cell interaction, a model for Tangier disease. 3) When the apolipoprotein-mediated HDL generation was blocked by probucol in the LCAT knock-out mice in which non-specific diffusion mediated efflux of cell cholesterol is impaired, cholesterol accumulated in certain organs as the liver and thymus.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Hidetosi Kotake et-al.: "Modification of the N-teruminal cystein of plasma cholesteryl ester transfer protein selectively inhibits triglyceride transfer activity" Biochim.Biophys.Acta. 1347. 69-74 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Koon K.Teo et-al: "cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis" Can.J.Cardiol.13. 591-599 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Qianqian Li et-al.: "Selective down-regulation by protein kinase C inhibitors of apolipoprotein-mediated cholesterol efflux in macrophages." Biochemistry. 36. 12045-12052 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Sinji Yokoyama: "Apolipoprotein-Mediated Cellular Cholesterol Efflux (review)" Biochim.Biophys.Acta. 1392. 1-15 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kannna Sasai et-al.: "Human cholesteryl ester transfer protein (CETP) measured by enzyme-linked immunosorbent assay with two monoclonal antibodies against rabbit CETP" Clinical Chemistry. 44. 1466-1473 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Lisa A.Main et-al.: "Cholesteryl ester transfer protein reaction between plasma lipoprotein" J.Biochemistry. 124. 237-243 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Jin-ichi Ito et-al.: "J.Neurochem." Differential generation of high density lipoprotein by Endogenous and exogenous apolipoproteins in cultured fetal rat astrocytes (in press), (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hidetosi Kotake et-al.: "Modification of the N-teruminal cystein of plasma cholesteryl ester transfer protein selectively inhibits triglyceride transfer activity" Biochim.Biophys.Acta. 1347. 69-74 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Koon K.Teo et-al.: "Rationale and designe features of a clinical trial examining the effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis" Can.J.Cardiol.13. 591-599 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Qianqian Li et-al.: "Selective down-regulation by protein kinase C inhibitors of apolipoprotein-mediated cholesterol efflux in macrophages" Biochemistry. 36. 12045-12052 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shinji Yokoyama: "Apolipoprotein-Mediated Cellular Cholesterol Efflux (review)" Biochim.Biophys.Acta. 1392. 1-15 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kanna Sasai et-al.: "Human cholesteryl ester transfer protein (CETP) measured by enzyme-linked immunosorbent assay with two monoclonal antibodies against rabbit CETP" Clinical Chemistry. 44. 1466-1473 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Lisa A.Main et-al.: "Cholesteryl ester tranfer protein reaction between plasma lipoprotein" J.Biochemistry. 124. 237-234 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Jin-ichi Ito et-al.: "Differential generation of high density lipoprotein by Endogenous and exogenous apolipoproteins in cultured fetal rat astrocytes" J.Neurochem.(in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shinji Yokoyama.: "Apolipoprotein-Mediated Cellular Cholesterol Efflux(review)." Biochim.Biophys.Acta. 1392. 1-15 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kanna Sasai et-al.: "Human cholesteryl ester transfer protein(CETP) measured by enzyme-linked immunosorbent assay with two monoclonal antibodies against rabbit CETP:" Clinical Chemistry. 44. 1466-1473 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Lisa A.Main et-al.: "Cholesteryl ester transfer protein reaction between plasma lipoproteins." J.Biochemistry. 124. 237-243 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Jini-ichi Ito,Li-Yong Zhang,Michiyo Asai and Shinji Y.: "Defferential generation of high density lipoprotein by endogenous and exogenous apolipoproteins in cultured fetal rat astrocytes." J.Neurochem.(in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Qiangian Li, Maki Tsujita, Shinji Yokoyama: "Selective doten-regulation by protein kinase Ciuhibitors of apolipoprotein-mediated cholesterol efflux in macrophages" Biochemistry. 36. 12045-12052 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hidetoshi Kotake, Luis B.Agellon, Shinji Yokoyama: "Modification of the N terminal Cystein of plasma cholestery ester transfer protein selectirely inhibits triglyceride transfer activity" Biochim.Biophys.Acta. 1347. 69-74 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Shinji Yokoyama: "Apolipoprotoin Mediated Cellula cholesterol Efflux" Biochim.Biophys.Acta. (in press). (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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