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Studies on the Mechanisms of Action of Antitumor and Membrane-Active Proteins Using Artificial Membranes (Liposomes)

Research Project

Project/Area Number 62570112
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field General medical chemistry
Research InstitutionThe University of Tokushima

Principal Investigator

YOSHIMURA Tetsuro  Institute for Enzyme Research, University of Tokushima, 酵素科学研究センター, 助教授 (30035472)

Co-Investigator(Kenkyū-buntansha) MAEZAWA Shigenori  Institute for Enzyme Research, University of Tokushima, 酵素科学研究センター, 助手 (70173698)
SONE Saburo  School of Medicine, University of Tokushima, 医学部附属病院, 講師 (40145024)
Project Period (FY) 1987 – 1988
Project Status Completed (Fiscal Year 1988)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1988: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1987: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsAntitumor Action / Membrane action / Membrane fusion / Phospholipid exchange between Membranes / Antitumor cytokine / Clathrin / Phospholipid exchange protein / リポソーム / 腫瘍壊死因子 / インターフェロン
Research Abstract

Studies on the Molecular Mechanisms of Action of Tumor Necrosis Factor (TNF) and Interferon (IFN) - TNF and IFN show cytotoxic efects on tumor cells. We found that TNF, IFN- and IFN- have perturbing actions on liposome membranes, that the differences in the membrane actions of these three cytokines are apparently consistent with the differential effects of these cytokines on tumor cells, and that their combined effects are synergistic, which are compatible with the synergisms in their cytotoxic effects, suggesting that membrane action may be important for expression of their cytotoxic activities. We next examined the effect of membrane lipid composition on the membrane actions of the three cytokines, and found that membrane phosphatidylserine modulates the mumbrane action of IFN- most prominently.
Studies on the Mechanism of Action of Clathrin in Receptor-Mediated Emdocytosis and Intracellular Protein Transport - Receptor-mediated endocytosis and intracellular protein transport are init … More iated by membrane fusion and membrane formation in the plasma membranes and intracellular membranes. We found that clathrin induces fusion of liposome membranes, and elucidated the molecular mechanism of membrane fusion induced by clathrin in vitro, providing the general mechanism of protein-induced membrane fusion. We next determined the molecular conformation of clathrin in solution and the fusion-active domains in the protein molecule, which implies the significant role of clathrin in the fusion of intracellular membranes.
Studies on the Mechanism of Phospholipid Exchange between Membranes mediated by Phospholipid Transfer Protein - Phospholipid transfer protein mediates phospholipid exchange between intracellular membranes. We studied the exchange reaction by the protein using liposome membrane systems, and developed the general kinetic model for the exchange reaction, which was verified experimentally. This model resolved the contradictory results observed previously, and permitted a quantitative interpretation of the reaction. Less

Report

(3 results)
  • 1988 Annual Research Report   Final Research Report Summary
  • 1987 Annual Research Report
  • Research Products

    (35 results)

All Other

All Publications (35 results)

  • [Publications] Tetsuro Yoshimura: Journal of Biological Chemistry. 262. 4597-4601 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 吉村哲郎: Therapeutic Research. 7. 72-77 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Tetsuro Yoshimura: Journal of Biochemistry(Tokyo). 101. 1265-1272 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 寺田弘: 膜. 13. 2-12 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Tetsuro Yoshimura: Biochemistry International. 17. 1157-1163 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Tetsuro Yoshimura: Archives of Biochemistry and Biophysics. 266. 299-312 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Shigenori Maezawa: Biochemistry. 28. (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Tetsuro Yoshimura: Biochimica et Biophysica Acta. (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Tetsuro Yoshimura: Biochemistry. (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 吉村哲郎: "生体コロイド研究法:膜融合の解析" 広川書店, (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Tetsuro Yoshimura: "Proceedings of the 2nd International Conference on TNF and Related Cytokines" Karger Pub., (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Tetsuro Yoshimura: "Different and Synergistic Actions of Human Tumor Necrosis Factor and Interferon- in Damage of Liposome Membranes" Journal of Biological Chemistry. 262. 4597-4601 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Tetsuro Yoshimura: "Molecular Mechanism for Expression of Antitumor Activity of TNF - An Approach Using a Liposome Membrane Model -" Therapeutic Research. 7. 72-77 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Tetsuro Yoshimura: "Exposure of Hydrophobic Domains of Clathrin in Its Membrane Fusion-Inducible pH Region" Journal of Biochemistry (Tokyo). 101. 1265-1272 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Hiroshi Terada: "Transfer of Bioactive Compounds into Biomembrane Systems and Induction of Their Biological Activities" Membrane. 13. 2-12 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Teturo Yoshimura: "Molecular Weight of Tumor Necrosis Factor Determined by Gel Permeation Chromatography Alone or in Combination with Low-Angle Laser Light Scattering" Biochemistry International. 17. 1157-1163 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Tetsuro Yoshimura: "General Kinetic Model for Protein-Mediated Phospholipid Transfer between Membranes" Archives of Biochemistry and Biophysics. 266. 299-312 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Shigenori Maezawa: "Mechanism of Protein-Induced Membrane Fusion: Fusion of Phospholipid Vesicles by Clathrin Associated with Its Membrane Binding and Conformational Change" Biochemistry. 28. (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Tetsuro Yoshimura: "Modulation of Membrane Perturbation Induced by Tumor Necrosis Factor,Interferons and by Phosphatidylserine" Biochimica et Biophysica Acta. (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Tetsuro Yoshimura: "Light Scattering Studies on the Molecular Conformation of Clathrin in Solution" Biochemistry. (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Tetsuro Yoshimura: Principles of Biological Colloid Research: Membrane Fusion Analysis. Hirokawa Publishing Co., (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Tetsuro Yoshimura: Proceedings of the 2nd International Conference on TNF and Related Cytokines. Karger Pub., (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Tetsuro Yoshimura: Biochemistry International. 17. 1157-1163 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Tetsuro Yoshimura: Archives of Biochemistry and Biophysics. 266. 299-312 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Shigenori Maezawa: Biochemistry. 28. (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] Tetsuro Yoshimura: Biochimica et Biophysica Acta. (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] Tesuro Yoshimura: Biochemistry. (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] 吉村哲郎: "生体コロイド研究法:膜融合解析" 広川書店, (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] Tesuro Yoshimura: "Proceedings of the 2nd International Conference on TNF and Related Cytokines" Karger Pub., (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] T. Yoshimura & S. Sone: Journal of Biological Chemistry. 262. 4597-4601 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] T. Yoshimura & S. Sone: Science.

    • Related Report
      1987 Annual Research Report
  • [Publications] 吉村哲郎: Therapeutic Research. 7. 72-77 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] T. Yoshimura;S. Maezawa;K. Hong: Journal of Biochemistry. 101. 1265-1272 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] S. Maezawa;T. Yoshimura;K. Hong;N. Duzgunes;D.Papahajopoulos: Biochimica et Biophysica Acta.

    • Related Report
      1987 Annual Research Report
  • [Publications] 寺田弘, 吉村哲郎: 膜. 13. 2-12 (1988)

    • Related Report
      1987 Annual Research Report

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Published: 1987-04-01   Modified: 2016-04-21  

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