1988 Fiscal Year Final Research Report Summary
Studies on the Mechanisms of Action of Antitumor and Membrane-Active Proteins Using Artificial Membranes (Liposomes)
| Project/Area Number |
62570112
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
General medical chemistry
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| Research Institution | The University of Tokushima |
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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)
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| 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)
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| Project Period (FY) |
1987 – 1988
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| Keywords | Antitumor Action / Membrane action / Membrane fusion / Phospholipid exchange between Membranes / Antitumor cytokine / Clathrin / Phospholipid exchange protein / リポソーム |
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| 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
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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
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Research Products
(22 results)
