| Project/Area Number |
04453130
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
応用生物化学・栄養化学
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
KITO Makoto Research Institute for Food Science, Professor, 食糧科学研究所, 教授 (60027183)
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| Co-Investigator(Kenkyū-buntansha) |
MORIYAMA Tatsuya Research Institute for Food Science, Instructor, 食糧科学研究所, 助手 (60239704)
URADE Reiko Research Institute for Food Science, Instructor, 食糧科学研究所, 助手 (90167289)
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 1993: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1992: ¥6,200,000 (Direct Cost: ¥6,200,000)
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| Keywords | Arachidonic acid / Phospholipids / Collagen / Human platelets / 小胞体プロテアーゼ / ER-60プロテアーゼ / タンパク質代謝 / ホスファチジルイノシトール / ホスファチジルセリン |
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| Research Abstract |
We have indicated that several nanomolar thromboxane A_2 (TXA_2) originating from inositollipids may directly cause Ca^<2+> mobilization in human platelets during activation with collagen.
The mechanism of arachidonic acid (AA) release in collagen-activated human platelets was studied. An arachidonic acid metabolite, thromboxane B_2, was formed in parallel with the formation of phosphatidic acid without fomation of lysophosphatidic acid or lysophosphatidylinositol in the absence of extracellular Ca^<2+>, suggesting that AA was released from PI via a PI-specific phospholipase C/diacylglycerol lipase/monoacylglycerol lipase pathway under the cytosolic low Ca^<2+> concentrations. Moreover, solubilized DG lipase and MG lipase could hydrolyze the substrates at basel cytosolic free Ca^<2+> concentrations. Subsequently, the relationship of cytosolic free Ca^2 concentrations and formation of AA metabolites was analyzed using Ca^<2+> ionophore, A23187. Collagen was able to induce a release of small amounts of AA under basal cytosolic Ca^<2+> conditions. However, a release of large amounts of AA was induced by phospholipase A_2 activated by both collagen-receptor occupancy and elevated Ca^<2+> levels. A TXA_2 mimetic agonist, STA_2 induced all the responses except for AA release. From these results, the mechanism of AA release and signal transduction in collagen-activated human platelets is discussed.
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