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Synthesis and application of functional domain of macrophage scavenger receptor

Research Project

Project/Area Number 10470494
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field 医薬分子機能学
Research InstitutionOsaka University

Principal Investigator

DOI Takefumi  Graduate School of Pharmaceutical Sciences Osaka University Professor, 薬学研究科, 教授 (00211409)

Co-Investigator(Kenkyū-buntansha) IMANISHI Takeshi  Graduate School of Pharmaceutical Sciences Osaka University Professor, 薬学研究科, 教授 (40028866)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥10,700,000 (Direct Cost: ¥10,700,000)
Fiscal Year 2000: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1999: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1998: ¥6,100,000 (Direct Cost: ¥6,100,000)
Keywordsmacrophage / scavenger receptor / model molecule / aggregation / HSP70 / HSP90 / GAPDH / phosphorylation / 細胞質ドメイン / フコイダン / LPS / NO産生 / アフィニティカラム / 機能ドメイン / ペプチド分子 / 核酸分子
Research Abstract

We have synthesized the ligand binding domain of macrophage scavenger receptor (MSR) and investigated the interaction of this molecule to polynucleotides and peptide fragments in apolipoprotein B-100. We found that a certain aggregate form of both polynucleotides and peptides modified by acetic acid or acrolein could compete the ligand binding of MSR.X-ray fiber diffraction analysis suggested that the competitive peptides modified by acrolein form a "cross β structure" as detected on amyloid β-peptide.
We have also synthesized the cytoplasmic domain of MSR.Affinity column with this domain was used for isolating the molecules to associate with MSR.By this column, HSP70, HSP90, aminopeptidase, S-adenosylhomocysteinase, glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and a unknown protein were isolated. We are now investigating the function of these proteins for signal transduction of MSR.
We have analized the point mutants of which each serine or threonine residue was substituted by alanine in cytoplasmic domain of MSR.We found that the serine 16, 16th amino acid residue from N-terminus of MSR, was a residue to be phosphorylated by protein kinase and to play an important role for the signal transduction through MSR.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] M.Honda: "Immunohistochemical evidence for a macrophage scavenger receptor in Mato cells and reactive microglia of ischemia and Alzheimer's disease."Biochem.Biophys.Res.Commun.. 245. 734-740 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Yamada: "Scavenger receptor family proteins : roles for atherosclerosis ; host defence and disorders of the central nervous system."Cell.Mol.Life Sci.. 54. 628-640 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] S.Obika: "Properties of cationic liposomes composed of cationic lipid YKS-220 having an ester linkage : adequate stability, high transtection efficiency, and low cytotoxicity."Biol.Pharm.Bull.. 22. 187-190 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Suzuki: "Oligonucleotide aggregates bind to the macrophage scavenger receptor."Eur.J.Biochem.. 260. 855-860 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Takakura: "Characterization of plasmid DNA binding and uptake by peritoneal macrophages from class A scavenger receptor knockout mice."Pharmaceutical Research. 16. 503-508 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Morimoto: "VXFD in the cytoplasmic domain of macrophage scavenger receptors mediates their efficient internalization and cell-surface expression."Biol.Pharm,Bull.. 22. 1022-1026 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] W.Yu: "Gene transfer mediated by YKS-220 cationic particles : convenient and efficient gene delivery reagent."J.Biochem (Tokyo). 125. 1034-1038 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Shirai: "Structure and function of type I and II macrophage scavenger receptors."Mech.Ageing Dev.. 111. 107-121 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.S.Liao: "Transcriptional inhibition by interleukin-6 of the class A macrophage scavenger receptor in macrophages derived from human peripheral monocytes and the THP-1 monocytic cell"Arterioscler.Thromb.Vasc.Biol.. 19. 1872-1880 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Honda, H.Akiyama, Y.Yamada, H.Kondo, Y.Kawabe, M.Takeya, K.Takahashi, H.Suzuki, T.Doi, A.Sakamoto, S.Ookawara, M.Mato, P.J.Gough, D.R.Greaves, S.Gordon, T.Kodama, & M.Matsushita: "Immunohistochemical evidence for a macrophage scavenger receptor in Mato cells and reactive microglia of ischemia and Alzheimer's disease."Biochem.Biophys.Res.Commun.. 245. 734-740 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Yamada, T.Doi, T.Hamakubo, & T.Kodama: "Scavenger receptor family proteins : roles for atherosclerosis, host defense and disorders of the central nervous system."Cell.Mol.Life Sci.. 54. 628-640 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] S.Obika, W.Yu, A.Shimoyama, T.Uneda, T.Minami, K.Miyashita, T.Doi, & T.Imanishi: "Properties of cationic liposomes composed of cationic lipid YKS-220 having an ester linkage : adequate stability, high transfection efficiency, and low cytotoxicity."Biol.Pharm.Bull.. 22. 187-190 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Suzuki, T.Doi. T.Imanishi, T.Kodama & T.Tanaka: "Oligonucleotide aggregates bind to the macrophage scavenger receptor."Eur.J.Biochem.. 260. 855-860 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Takakura, T.Takagi, M.Hashiguchi, M.Nishikawa, F.Yamashita, T.Doi, T.Imanishi, H,Suzuki, T.Kodama, & M.Hashida: "Characterization of plasmid DNA binding and uptake by peritoneal macrophages from class A scavenger receptor knockout mice."Pharmaceutical Research. 16. 503-508 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Morimoto, Y.Wada, J.Hinagata, T.Imanishi, T.Kodama, & T.Doi: "VXFD in the cytoplasmic domain of macrophage scavenger receptors mediates their efficient internalization and cell-surface expression."Biol.Pharm.Bull.. 22. 1022-1026 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] W.Yu, A.Shimoyama, T.Uneda, S.Obika, K.Miyashita, T.Doi, & T.Imanishi: "Gene transfer mediated by YKS-220 cationic particles : convenient and efficient gene delivery reagent."J.Biochem., (Tokyo). 125. 1034-1038 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Shirai, T.Murakami, Y.Yamada, T.Doi, T.Hamakubo & T.Kodama: "Structure and function of type I and II macrophage scavenger receptors."Mech.Ageing Dev.. 111. 107-121 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.S.Liao, A.Matsumoto, H.Itakura, T.Doi, M.Honda, T.Kodama, & Y.J.Geng: "Transcriptional inhibition by interleukin-6 of the class A macrophage scavenger receptor in macrophages derived from human peripheral monocytes and the THP-1 monocytic cell line."Arterioscler.Thromb.Vasc.Biol.. 19. 1872-1880 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] S.Obika: "Symmetrical Cationic Triglycerides : An Efficient Synthesis and Application to Gene Transfer"Bioorg.Med.Chem.. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] K. Suzuki: "Oligonucleotide aggregates bind to the macrophage scavenger receptor"Eur. J. Biochem.. 260. 855-860 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K. Morimoto: "VXFD in the Cytoplasmic Domain of Macrophage Scavenger Receptors Mediates Their Efficient Internalization and Cell-Surface Expression"Biol. Pharm. Bull.. 22. 1022-1026 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] M.Honda: "Immunchistochemical Evidence for a Macrophage Scavenger Receptor in Mato Cells and Reactive Microglia of Ischemia and Alsheimer's Disease" Biochem.Biophys.Res.Commun.245. 734-740 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Y.Yamada: "Scavenger receptor family proteins: roles for atherosclerosis,host defence and disorders of the central nervous system" Cell.Mol.Life Sci.54. 628-640 (1998)

    • Related Report
      1998 Annual Research Report

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

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