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1995 Fiscal Year Final Research Report Summary

Structure and function of macrophage scavenger receptors

Research Project

Project/Area Number 06557054
Research Category

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

Allocation TypeSingle-year Grants
Research Field 内分泌・代謝学
Research InstitutionUniversity of Tokyo

Principal Investigator

KODAMA Tatsuhiko  The Third Department of Internal Medicine, University of Tokyo, 医学部(病), 助手 (90170266)

Co-Investigator(Kenkyū-buntansha) KITA Toru  Dept.Gerontology, Univ.Kyoto, 医学部, 教授 (60161460)
DOI Takefumi  Pharmacetical Science, Univ.Osaka, 薬学部, 助教授 (00211409)
WADA Yoichiro  3rd Dept.Int.Med, Univ.Tokyo, 医学部(病), 医員
NAKAJIMA Atsushi  3rd Dept.Int.Med, Univ.Tokyo, 医学部(病), 医員
MATSUHASHI Nobuyuki  3rd Dept.Int.Med, Univ.Tokyo, 医学部(病), 助手 (10221590)
Project Period (FY) 1994 – 1995
Keywordsmicrophage / scavenger recepto / atherosclerosis / lipoprotein / host defense / mouse genetics / endocytosis / adhesion molecule
Research Abstract

In order to develop a novel therapeutic approach, over 600 novel type of lipophilic antioxidants were synthesized and analyzed. Some of them are very potent to prevent oxidation of LDL in vitro and were absorbed well by experimental animals without any serious side effects. Two of them, LDL-antioxidant 1 (LAO-1) and LAO-2 were analyzed in WHHL rabbits, mice model of atherosclerosis and post PTCA stenosis model in rabbits. These drugs (LAO-1and2) are useful for the prevention of atherosclerosis in WHHL rabbits and also for the prevention of atherosclerosis in C57BL6-high cholestarol diet model. These compounds inhibit the the development of post-baloon injury stenosis. The growth of vascular smooth muscle cell after the cytokine stimulation was inhibited by these compounds. Probucol, an potent LDL antioxidant was effective for the prevention of WHHL rabbit atherosclerosis, but probucol exaggerated the atherosclerosis in LDL receptor deficient mice and apo E deficient mice, which was not seen after LAO-1 or 2 administration.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Mato, M, Kodama, T et al: "Involvement of specific macrophage lineage cells surrounding arterioles in barrier and scavenger function in brain cortex." Proc. Natl. Acad. Sci USA.(in press). (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Terauchi, Y, Kodama T et al: "Pancreatic B-cell-specific targeted disruption of glucokinase gene." J Biol. Chem.270. 30253-30256 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shimokawa, T. Kodama T et al: "Determination of mRNA levels of cholesterol biosyntheis enzymes and LDL receptor using ribonuclease protection assay." J. Lipid Res.36. 1919-1924 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kume, S. et al: "Immunohistochemical and ultrastructral detection of advanced glycation end products in atherosclerotic lesions of human aorta with a novel specific monoclonal antibody" Am. J. Patol.654-667 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Araki, N, et al: "Macrophage scavenger receptor mediates the endocytic uptake and degradation of advanced glycation end products of the maillard reaction" Eur. J. Biochem. 230. 408-415 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Wada, Y, et al: "Structure and function of macrophage scavenger receptors" Ann. N. Y. Acad. Sci.748. 226-239 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mato, M., Ookawara, S., Sakamoto, A., Aikawa, E., Ogawa, T., Mitsuhashi, U., Masuzawa, T., Suzuki, H., Honda, M., Yazaki, Y., Watanabe, E., Luoma, J.Yla-Herttuala, S., Fraser, I., Gordon, S.and Kodama, T: "Involvement of specific macrophage lineage cells surrounding arterioles in barrier and scavenger function in brain cortex." Proc.Natl.Acad.Sci USA. (in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Terauchi Y,Sakura H,Yasuda K,Iwamoto K,Takahashi N,Ito K,Kasai H,Suzuki H,Ueda O,Kamada N,Jishage K,Komada K,Noda M,Kanazawa Y,Taniguchi S,Miwa I,Akanuma Y,Kodama T,Yazaki Y and Kadowaki T: "Pancreatic B-cell-specific targeted disruption of glucokinase gene" J.Biol.Chem.270. 30253-6 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shimokawa, T., Kawabe, Y., Honda, M., Yazaki, Y., Itakura, H and Kodama T: "Determination of mRNA levels of cholesterol biosynthesis enzymes and LDL receptor using ribonuclease protection assay" J.Lipid Res.(in press). (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kume, S., Takeya, T., Mori, T., Araki, N., Suzuki, H., Horiuchi, S., Kodama, T., Miyauchi, Y.and Takahashi, K.Am: "Immunohistochemical and ultrastructural detection of advanced glyc ation end products in atherosclerotic lesions of human aorta with a novel specific monoclonal antibody" J.Patol. 654-667 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Araki, N., Higashi, T., Mori, T., Shibayama, R., Kawabe, Y., Kodama, T., Takahashi, K., Shichiri, M., and Horiuchi, S: "Macrophage scavenger receptor mediates the endocytic uptake and degradation of advanced glycation end products of the maillard reaction" Eur.J.Biochem. 230. 408-415 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Wada, Y,.Doi.T,Kodama.T.et al: "Structure and function of macrophage scavenger receptors" Ann.N.Y.Acad.Sci.748. 226-239 (1995)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1997-03-04  

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