| Project/Area Number |
09672346
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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 |
Laboratory medicine
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| Research Institution | Asahikawa Medical College |
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Principal Investigator |
HAYASHI Yukiko (1999-2000) Asahikawa Medical College, Dept. of Medicine, Assistant Prof, 医学部, 講師 (50125407)
池田 久實 (1997-1998) 旭川医科大学, 医学部, 教授 (90091561)
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| Co-Investigator(Kenkyū-buntansha) |
KOHMURA Chikashi Asahikawa Medical College, Dept. of Medicine, Instructor, 医学部, 助手 (40261408)
KAWABATA Isao Asahikawa Medical College, Dept. of Medicine, Instructor, 医学部, 助手 (50195129)
林 由紀子 旭川医科大学, 医学部, 講師 (50125407)
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| Project Period (FY) |
1997 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | Platlet / Signal transduction / PKC / Arachidonic acid / CD36 / PUFA / 膜蛋白CD36 / 多価不飽和脂肪酸 |
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| Research Abstract |
We have studied the effects of platelet membrane protein CD36 on the platelet signal transduction using CD36 defective platelets. One of the reported roles of CD36 is the transporter of unsaturated fatty acids. Compared to normal ones little characteristic responses of CD36 defective platelets have been reported. Arachidonic acid (AA), one of the unsaturated fatty acid, has pivotal role in platelet aggregation through its metabolite TxA2. We observed that under the decreasing store Ca2+ conditions CD36 defective platelets showed clear differences in the reactions where AA metabolites have more essential roles. We found that AA inhibits platelet aggregation induced by its metabolites TxA2. The IC50 of AA for normal platelets was 26.5±12.2 μM,and that for C36 defective platelets was 105±44 μM respectively. These results corroborate the role of CD36 as fatty acid transporter. This is the first report on the impaired functions of CD36 defective platelets. AA and other unsaturated fatty acids activate Ca2+ independent PKC in the cytosol independently of membrane lipids and cytosolic Ca2+ Physiological significances of the PKC isotypes have not been clearly understood. Hence the mechanisms of the inhibiting effects of AA were next studied. It was confirmed that AA inhibits PLCβ activation through serine phosphorylation by Ca2+ independent PKC.Consequently the Ca2+ dependent PKC closely connected to aggregation are not activated. Thus PKC isotypes are linked to each other leading to the physiologically proper responses of platelets. More important point is that AA itself regulates reactions induced by its descendants through the PKC isotypes.
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