| Project/Area Number |
09470045
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
TAKESHIGE Koichiro KYUSHU UNIVERSITY, Factory of Medicine, Prof., 大学院・医学研究院, 教授 (10037450)
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| Co-Investigator(Kenkyū-buntansha) |
YAMASAKI Soh KYUSHU UNIVERSITY, Factory of Medicine, Assistant, 大学院・医学研究院, 助手 (70315084)
MUTA Tatsushi KYUSHU UNIVERSITY, Factory of Medicine, Ass.Prof., 大学院・医学研究院, 助教授 (60222337)
SUMIMOTO Hideki KYUSHU UNIVERSITY, Factory of Medicine, Prof., 大学院・医学研究院, 教授 (30179303)
栗林 太 九州大学, 大学院・医学系研究科, 助手 (60251443)
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| Project Period (FY) |
1997 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥8,000,000 (Direct Cost: ¥8,000,000)
Fiscal Year 2000: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1999: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1998: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | superoxide / active oxygens / neurophils / NADPH oxidase / Rac / p47^<phox> / p67^<phox> / p40^<phox> / 食細胞 / SH3ドメイン |
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| Research Abstract |
The neutrophil NADPH oxidase, dormant in resting state, is activated to produce superoxide, which is a precursor of other active oxygens which involved in killing of phagocytozed bacteria and in inflammation. The NADPH oxidase consists of a membrane-integrated flavocytochrome b_<558> comprising two subunits, gp91^<phox> and p22^<phox>. Activation of the oxidase occurs when two cytosolic SH3 domain-containing factors, p47^<phox> and p67^<phox>, the small GTP-binding protein Rac and another cytosolic factor, p40^<phox>, assemble and translocate to the plasma membrane. In addition, the cytosolic factors are phosphorylated during oxidase activation. The assembly process is regulated and involves multiple binding interactions between the oxidase factors, resulting in an active oxidase complex. It has been demonstrated in this study that the specific molecular interactions occuring between p47^<phox> and cytochrome b_<558>, p67^<phox> and Rac, and p40^<phox> and p67^<phox>, leading to activation of the oxidase.
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