| Project/Area Number |
08672551
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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 | National Institute of Health Sciences (NIHS) |
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Principal Investigator |
SUZUKI Kazuhiro NIHS,Div.of Xenobiotic Metabolism and Disposition, Section Chief, 代謝生化学部, 室長 (10154527)
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| Co-Investigator(Kenkyū-buntansha) |
ADACHI Reiko NIHS,Div.of Xenobiotic Metabolism and Disposition, Researcher, 代謝生化学部, 研究員 (10291113)
KASAHARA Tadashi Kyoritsu College of Pharmacy, Dept.of Biochemistry, Professor (60049096)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1997: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Cofilin / Phagocytes / Opsonized zymosan / Okadaic acid / Superoxide / Cytoskeleton / Intracellular pH / Translocation / 細胞内pH変化 / F-アクチン / オカダ酸 |
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| Research Abstract |
Cofilin, an actin/PLP2-binding phosphoprotein, plays important roles in various cells and tisssues through cytoskeletal reorganization. We studied the roles of cofiln in phagocyte functions using neutrophil-like HL-60 cells and macrophage-like U937 cells. Our major results are as follows :
(1)Opsonized zymosan (OZ) induced rapid dephosphorylation of cofilin and its translocation to plasma membranes on which superoxide was generated and/or OZ particles were engulfed.
(2)Okadaic acid (OA) which is a potent inhibitor for phosphoprotein phosphatase type 2A and type 1, did not inhibit the stimulus-dependent dephosphorylation and translocation of cofilin at 1muM, an enhancing concentration for OZ-induced superoxide production,
(3)To the contrary, OA 5muM, an inhibitory concentration for the OZ-induced respiratory burst, inhibited completely the stimulus-dependent dephosphorylation and translocation of cofilin.
(4)OZ induced decrease in intracellular pH in differentiated U937 cells from 7.3 to 6.8. In the phagocytes, the changes in pH may be an important factor that regulate the F-actin-depolymerizing activity of cofilin.
These results suggest that the stimuli-dependent dephosphorylation and translocation of cofillin are crucial for the activation of phagocytes.
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