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Reaction mechanism of cholesterol transport system

Research Project

Project/Area Number 05044173
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research InstitutionKagawa Medical School

Principal Investigator

ICHIKAWA Yoshiyuki  Kagawa, Medical School, Professor, 医学部, 教授 (60028355)

Co-Investigator(Kenkyū-buntansha) YAMAMURA Taku  Research Institute of National Cardiovascular Center, Head, 病因部, 室長 (20132938)
YAMAMOTO Akira  Research Institute of National Cardiovascular Center, Vice Director, 副所長 (00028408)
YOKOYAMA Shinji  University of Alberta, Professor, 医学部, 教授 (10142192)
OHNISHI Taira  Kagawa, Medical School, Associate Professor, 医学部, 助教授 (50211107)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥8,000,000 (Direct Cost: ¥8,000,000)
Fiscal Year 1994: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1993: ¥4,000,000 (Direct Cost: ¥4,000,000)
KeywordsCholesterol Reverse Transport System / Apolipoprotein / Lipid Microemulsion / Pyrene Compound / Vascular smooth muscle cell / Cholesterol efflux / Discoidal Highdensity Plasma Lipoprotein / ディスコイダルHDL
Research Abstract

The initial step of reverse cholesterol transport from peripheral cells to liver cells is the efflux of cholesterol from peripheral cells. We revealed that the addition of free apolipoprotein induces the efflux of cholesterol from macrophage and smooth muscle cells and free apolipoprotein is incorporated into newly synthesized discoidal HDL-like particle. At the next step, free cholesterol is converted to cholesteryl ester by LCAT and then cholesteryl ester is transferred among various lipoproteins by plasma lipid transfer protein (LTP). In this term, our study of reverse cholesterol transport was focused on the action of LCAT and the effect of apolipoproteins on the LTP reaction.
We revealed that the LTP reaction requires the presence of apolipoprotein (A-I,A-II,C-III and E)on the surface of lipid particle and the mode of integration of apolipoprotein into the surface lipid regulates the lipid selectivity of the LTP reaction. In addition, the effect of A-IV on the LTP reaction was also … More studied and the effect was revealed to be essentially the same as other apolipoproteins.
We prepared the monoclonal antibody against rabbit LTP,and we found the special clone which inhibit only triglyceride transfer by LTP.To clarify the structural basis of lipid selectivity of LTP,we decided to use molecular biological approach to characterize LTP.The cDNA of rabbit LTP was prepared and LTP was expressed in the yeast system. We are going to characterize the epitope of the clone using the expression system.
The transfer of free cholesterol between cell and HDL is thought to be concentration-dependent on the basis of equilibrium. The conversion of free cholesterol into cholesteryl ester by LTP causes the decrease of the concentration of free cholesterol in HDL and the decrease gives the driving force to the reverse cholesterol system. Our study revealed that the addition of LCAT into the macrophage system, where cholesterol efflux from cell is mediated by discoidal HDL-like particle or HDL,induces the decrease of free cholesterol and increase of cholesteryl ester in HDL,however, efflux of cholesterol remains to be unchanged. Further study must be necessary to establish the new theory of the mechanism of cholesterol efflux. Less

Report

(2 results)
  • 1994 Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Taira Ohnishi: "Selective transfer of cholesteryl ester over triglyceride by human plasma lipid transfer protein between apolipoprotein-activated lipid microemulsions." Biochemistry. 33. 4533-4542 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Taira Ohnishi: "Propertics of human plasma lipid transfer protein in aqueous solution and at interfaces." Biochemistry. 33. 6093-6099 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kerry W.S.Ko: "Triglyceride transfer is required for net cholesteryl ester transfer between lipoproteins in plasma by lipid transfer protein." Int.Biol.Chem.269. 28206-28213 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Taira Ohnishi: "Modulationof substrate selectivity in plasma lipid transfer protein reaction over structural variation of lipid particle." Biochim.Biophys.Acta. 1254. 126 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Helena Czarnecks: "Lecithin:Cholesterol acyltransferase reaction on cellular lipid released by free apolipoprotein-mediated efflux." Biochemistry. (in print). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Taira Ohnishi: "Selective transfer of cholesteryl ester over triglyceride by human plasma lipid transfer protein between apolipoprotein-activated lipid microemulsions." Biochemistry. 33. 4533-4542 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Taira Ohnishi: "Propertics of human plasma lipid transfer protein in aqueous solution and at interfaces." Biochemistry. 33. 6093-6099 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kerry W.S.Ko: "Triglyceride transfer is required for net cholesteryl ester transfer between lipoproteins in plasma by lipid transfer protein." Int.Biol.Chem.269. 28206-28213 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Taira Ohnishi: "Modulationof substrate selectivity in plasma lipid transfer protein reaction over structural variation of lipid particle." Biochim.Biophys.Acta. 1254. 117-126 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Helena Czarnecks: "Lecithin : Cholesterol acyltransferase reaction on cellular lipid released by free apolipoprotein-mediated efflux." Biochemistry. (in print). (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ohnishi,Taira: "Activation of human plasma lipid transfer protein by apolipoproteins." Biochemistry. 32. 5029-5035 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ko,Kerry W.S.: "Purification,characterization,and conformational analysis of rabbit plasma lipid transfer protein." Biochemistry. 32. 6729-6736 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Li,Qianqian: "Cholesterol is poorly available for free apolipoprotein-mediated cellular lipid efflux from smooth muscle cells." Biochemistry. 32. 4597-4603 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Czarnecka,Helena: "Regulation of lecithin-cholesterol acyl-transferase reaction by acyl acceptors and demonstration of its “idling" reaction." J.Biol.Chem.286. 19334-19340 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ohnishi,Taira: "Photoaffinity labeling of cytochrome P-450_<11>β with methyltrienolone as a probe for the substrate binding region." Biochim.Biophys.Acta. 1161. 257-264 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ohnishi,Taira: "Selective transfer of cholesteryl ester over triglyceride by human plasma lipid transfer protein between apolipoprotein-activated lipid microemulsions." Biochemistry. (in print). (1994)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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