| Project/Area Number |
18590408
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Parasitology (including Sanitary zoology)
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
TAKAKUWA Yuichi Tokyo Women's Medical University, School of Medicine, Professor (40113740)
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| Co-Investigator(Kenkyū-buntansha) |
MANNO Sumie Tokyo Women's Medical University, School of Medicine, Senior Lecturer (10101205)
NUNOMURA Wataru Tokyo Women's Medical University, School of Medicine, Assistant Professor (70256478)
KOSHINO lchiro Tokyo Women's Medical University, School of Medicine, Assistant Professor (80328377)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | malaria / erythrocyte / membrane lipid / raft / asymmetric distribution / membrane property / invasion |
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| Research Abstract |
In the present study, the necessary/sufficient conditions for erythrocyte invasion by malaria parasites were explored with respect to erythrocyte membrane lipid dynamism. To address this issue, effects of : i) Disruption and restoration of rafts without affecting membrane lipid content (incorporation of lidocaine into the membrane and following removal, respectively), ii) Cholesterol depletion (methyl- β -cyclodextrin (MBCD) treatment), iii) Sphingomyelin depletion (sphingomyelinase (SMase) treatment), of the erythrocyte membranes on the integrity of raft structure and signal transduction were examined. Importance of rafts in invasion by malaria parasites was studied using these lipid-modified erythrocytes.
Lidocaine treatment reversibly modulated raft structure, while MBCD and SMase treatments irreversibly modulated rafts. Lidocaine treatment also modulated signal transduction reversibly. Lidocaine treatment (disruption of rafts) reduced parasite growth rate. After removal of lidocaine (restoration of rafts) parasite growth rate was recovered. Invasion assay using synchronized schizonts showed that parasite invasion was almost completely inhibited in the presence lidocaine at 2 mM or higher. Altogether, it was suggested that malaria parasites utilize signal transduction pathway accumulated in rafts, for which lateral lipid dynamism is involved, to invade erythrocytes.
It is likely that malaria parasites induce PICA phosphorylation of some erythrocyte membrane skeletal proteins via Gsa-mediated process where lateral lipid dynamism is involved, facilitating membrane invagination that is the prerequisite for invasion. Lidocaine has already been applied to clinical use as local and systemic anesthetics. Novel therapy for malaria based on the reversible interruption of the raft-dependent signal transduction by lidocaine would be possible.
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