| Project/Area Number |
15590090
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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 |
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Principal Investigator |
SUZUKI Kazuhiro NIHS, Division of Biosignaling, Section chief, 代謝生化学部, 室長 (10154527)
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| Co-Investigator(Kenkyū-buntansha) |
ADACHI Reiko NIHS, Division of Biosignaling, Senior researcher, 代謝生化学部, 主任研究官 (10291113)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | neutrophil / HL-60 cell / chemotaxis / cofilin / phosphorylation / Interleukin-8 / PI3-kinase / siRNA / 食細胞 / siRNA |
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| Research Abstract |
Cofilin is a ubiquitous actin-binding protein. Only unphosphorylated cofilin binds actin and severs or depolymerizes a filamentous actin(F-actin) and cofilin is phosphrylated by LIM-kinase, a specific kinase of cofilin, to be an inactive form which does not bind actin. The phosphorylated cofilin is dephosphorylated by slingshot, a specific phosphatase, to be an active form. Recently we have reported that cofilin plays regulatory roles in superoxide production and phagocytosis by phagocytes. In this study, the roles of cofilin hi chemotaxis of leukocytes were investigated. Interleukin 8(IL-8), a potent physiological chemokine, triggered quick dephoshorylation and subsequent rephosphorylation of cofilin. The phosphorylation of cofilin was inhibited by S3-R peptide which consisted of a membrane-permeable peptide and a peptide of phosphorylation site of cofilin. When the S3-R peptide was introduced into neutrophil-like HL-60 cells, the chemotactic activity was enhanced while control peptide which contained an inverted sequence of phosphorylation site of cofilin did not such an enhancing effect. Wortmannin and LY294002,inhibitors of PI3 kinase, suppressed the chemotaxis and phosphorylation turnover of cofilin. On the other hand, siRNA of cofilin caused down-regulation of cofilin and inhibited the chemotaxis. Based on these results it is suggested that unphosphrylated active cofilin plays a critical role in the chemtaxis of phagocytes and PI3-kinase is involved in the control of phosphorylation/dephosphorylation cycle of cofilin.
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