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Development of new drug therapy for atherosclerosis

Research Project

Project/Area Number 06557058
Research Category

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

Allocation TypeSingle-year Grants
Research Field 内分泌・代謝学
Research InstitutionOsaka University

Principal Investigator

KAWATA Sumio  Osaka Univ.Med.Sch., Associate Professor, 医学部, 助教授 (90183285)

Co-Investigator(Kenkyū-buntansha) NAKANO Hirofumi  Kyowa Hakko, Tokyo Institute, Chief Administrator, 東京研究所, 管理室長
TAMURA Shinji  Osaka Univ.Med.Sch., Assistant, 医学部, 助手 (30243223)
YAMASHITA Shizuya  Osaka Univ.Med.Sch., Assistant, 医学部, 助手 (60243242)
TAKEMURA Kaoru  Osaka Univ.Med.Sch., Assistant Professor, 医学部, 講師 (00161240)
MATSUZAWA Yuji  Osaka Univ.Med.Sch., Professor, 医学部, 教授 (70116101)
中村 正  大阪大学, 医学部, 助手 (90252668)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥7,600,000 (Direct Cost: ¥7,600,000)
Fiscal Year 1995: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1994: ¥6,000,000 (Direct Cost: ¥6,000,000)
KeywordsAtherosclerosis / Vascular smooth muscle cells / Ras p21 / Farnesyl ; protein transferase / manumycin / Rasp21 / ファネルシルトランスフェラーゼ / 酵素阻害剤 / HPLC / 血管平滑筋細胞 / 増殖抑制
Research Abstract

Migration and proliferation of vascular smooth muscle cells (VSMC) play important roles in development of atherosclerosis. The migration and proliferation of VSMC are known to be stimulated by growth factors. Ras p21 is a key component in intracellular signal transduction pathway for cell growth via growth factor receptors.
Farnesylation of C-terminal of Ras p21 is required for its function as signal transducer. This farnesylation Ras p21 is catalyzed by farnesyl : protein transferase.
In this project, we examined inhibitory effects of manumycin, a potent farnesyl : protein transferase inhibitor, on VSMC growth in vitro and in vivo. Manumycin inhibited VSMC proliferation in vitro. Then, we administered manumycin to rats with balloon injury in carotid arteries. As a result, this inhibitor significantly suppressed intimal thickening in injured carotid arteries.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] J. Miyagawa,S. Kawata,et al.: "Localization of hoparin-binding EGF-like growth factor in the smooth muscle cells and macrophages of human atherosclerotic plaques." J. Clin. Invest.95. 404-411 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K. Fukuda,S. Kawata,et al.: "Increased mitogenic response to heparin-binding epidermal growth factor-like growth factor in vascular smooth muscle cells of diabetic rats." Arterioscler. Thromb. Vasc. Biol.15. 1680-1687 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H. Ishiguro,S. Kawata,et al.: "High-performance liquid chromatographic assay for farnesyl : protein transterase activity with dabsylated peptide." J. Chromatogr. B. 663. 35-42 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T. Nagase,S. Kawata,et al.: "Inhibition of cell growth of human hepatoma cell line (Hep G2) by a farnesyl : protein transferase inhibitor : a preferential suppression of Ras farnasylation." Int. J. Cancer. (in press). (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T. Ito,S. Kawata,et al.: "Suppression of human pancreatic cancer growth in BALB/c made mice by manumycin,a farnesyl : protein transterase inhibitor." Jpn. J. Cancer Res.(1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 河田純男 他: "ファーネシルピロホスフェイト" The Lipid. 6. 73-81 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 河田純男 他: "分子動脈硬化学" メディカル レビュー社, 363 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] J.Mijagawa, S.Kawata, et al.: "Localization of heparin-binding EGF-like growth factor in the smooth muscle cells and macrophages of human atherosclerotic plaques." J.Clin.Invest.95. 404-411 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K.Fukuda, S.Kawata, et al.: "Increased mitogenic response to heparin-binding epidermal growth factor-like growth facotr in vascular smooth muscle cells of diabetic rats." Arterioscr.Thromb.Vasc.Biol.15. 1680-1687 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H.Ishiguro, S.Kawata, et al.: "High-performance liquid chromatographic assay for farnesyl : protein transferase activity with dabsylated peptides." J.Chromatogr.B. 663. 35-42 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Nagase, S.Kawata, et al.: "Inhibition of cell growth of human hepatoma cell line (Hep G2) by a farnesyl : protein transferase inhibitor : a preferential suppression of Ras farnesylation." Int.J.Cancer. (in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Ito, S.Kawata, et al.: "Suppression of human pancreatic cancer growth in BALB/c nude mice by manumycin, a farnesyl : protein transferase inhibitor." Jpn.J.Cancer Res.(in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H.Ishiguro,et al.: "High-performance liquid chrom,atographic assay for farnesyl:protein transferase activity with dabsylates peptide." J.Chromatogr.B. 663. 35-42 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] S.Kawata,et al.: "Modulation of the mevalonate pathway and cell growth by pravastation and d-limonene" Br.J.Cancer. 69. 1015-1020 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] J.Miyagawa et al.: "Localization of heparin-binding EGF-like grouwth farton in the smeeth muscle cells and macrophages of human・・・" J.Chin.Invest. 95. 404-411 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 河田 純男 他: "血清脂質、ファーネシルピロホスフェイト。" The Lipid. 6. 73-81 (1995)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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