2007 Fiscal Year Final Research Report Summary
ldentifcation of the secretion mechanism of lipid mediators from the cells
| 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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| Keywords | transporter / ATPase / lipid mediator / orphan transporter / sphinoosine 1-phosphate / platelet / inside-out vesicle |
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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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[Journal Article] Sphingosine 1-phosphate is released from the cytosol of rat platelets in a carrier-mediated manner2006
Author(s)
N., Kobayashi, T., Nishi, T., Hirata, A., Kihara, T., Sano, Y., Igarashi, A., Yamaguchi
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Journal Title
Journal of Lipid Research 47
Pages: 614-621
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Characterization of mouse ABCA5 protein2006
Author(s)
M., Ohigashi, T., Nishi, A., Yamaguchi
Organizer
5th 21st Century COE "Towards Creating New" Industries Based on Inter-Nanoscience International Symposium
Place of Presentation
Awaji
Year and Date
20061200
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Characterization of mouse ABCA5 protein2006
Author(s)
M. Ohigashi, T. Nishi, A. Yamaguchi
Organizer
5th 21st Century COE "Towards Creating New Industries Based on Inter-Nanoscience" International Symposium
Place of Presentation
淡路
Year and Date
2006-12-22
Description
「研究成果報告書概要(和文)」より
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