| Project/Area Number |
18570128
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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 |
Functional biochemistry
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| Research Institution | Osaka University |
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Principal Investigator |
NISHI Tsuyoshi Osaka University, ISIR, Specialy Appointed Assistant Professor (60403002)
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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 |
¥4,110,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | transporter / ATPase / lipid mediator / orphan transporter / sphinoosine 1-phosphate / platelet / inside-out vesicle / 放出 / スフィンゴシン1リン酸 |
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| Research Abstract |
Intercellular signal transduction is the important system for the cell-cell communication in the highly organized living organism. Lipophilic compounds such as steroid hormones and lipid mediators are one of the most popular signaling molecules. However, little is known about how are these molecules exported from the cells. We are trying to identify the secretion mechanism and to isolate the transporters that are directly transporting these lipophific molecules. For this purpose, we are focusing to identify the sphingosine-1-phosphate (S1P) secretion system from the platelet. S1P is the lipid mediators that are playing important roles in cell migration, proliferation and apoptosis. So far, we were identified that S1 P is located in the inner leaflet of the plasma membrane and is showed thrombin or Ca^<2+> dependent secretion from the platelet. Using the transporter specific inhibitors, we proposed that ABC A-type transporters might participate the export of sphingosine-1-phosphate. Among the ABCA type transporters, we showed that ABCA7 is predominantly expressed in platelet. These results suggested that ABCA7 should be a candidate of sphingosine-1-phosphate transporter. To prove this hypothesis, we have been constructing the ABCA7 knock-out mice. We also identified that erythrocyte is synthesized the S1P and S1P is secreted from the cell without any stimuli. We prepared the inside-out membrane vesicle from rat erythrocyte and success to measure the S1 P transport activity. This S1P transport was ATP dependent manner and inhibited with glyburide and vanadate but not with other inhibitors for transporters or ionophores. These results strongly suggested the presence of transporter mediated S1P export system in rat erythrocyte.
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