Regulation of Cell death through P2X7 receptor activation in splenocytes
| Project/Area Number |
17590061
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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 |
Biological pharmacy
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| Research Institution | University of Shizuoka |
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Principal Investigator |
HARADA Hitoshi University of Shizuoka, Department of Pharmaceutical Sciences, Lecturer (30208681)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | P2X7 receptor / Cell death / T cell / Chloride ion |
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| Research Abstract |
Background. The P2X7 receptor is responsible for ATP or NAD-dependent cell death of murine T lymphocytes through the formation of membrane pores permeable to large molecules. In this study, we investigated P2X7 receptormediated cell death during murine T cell maturation.
Methods. Pore formation and cell death were assayed by ethidium and propidium uptake into cells, respectively. Exposure of phosphatidylserine on the outside surface of the cell membrane was detected by annexin V binding. Cell size was determined by the change in forward light scattering property on a flow cytometer.
The activity of P2X7 receptors, as measured by induction of cell death and pore formation, was higher in splenocytes than thymocytes. Flow cytometric analysis revealed that cell shrinkage was induced by activation of the P2X7 receptor in murine lymphocytes and the responding cells were T cells. Splenic T cells were more responsive than their thymic counterpart. NAD also induced T cell death and much higher ATP than NAD concentrations were required to induce pore formation and phosphatidylserine exposure. NAD did not induce cell shrinkage even in CD4+CD25+ T cells, which are more sensitive to death induction by P2X7 receptor signaling than conventional T cells. Moreover, decreased extracellular Cl-suppressed ATP-induced cell shrinkage and cell death, but not pore formation and phosphatidylserine exposure.
Conclusion. These observations indicate that the induction system of cell death by ATP and NAD through P2X7 receptor in T cells could be modulated during T cell maturation and the signaling pathways by ATP and NAD to lead cell death are not the same. The balance between ATP and NAD could play an important role in P2X7 receptor-mediated function of peripheral T lymphocytes.
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Report
(4 results)
Research Products
(33 results)
