Activation of the phagocyte NADPH oxidase and its disorders

吞噬细胞 NADPH 氧化酶的激活及其紊乱

• 批准号: 09470045
• 负责人: TAKESHIGE Koichiro
• 金额: $ 5.12万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-09470045/
• 关键词: superoxide; active oxygens; neurophils; NADPH oxidase; Rac; p47^<phox>; p67^<phox>; p40^<phox>; 食細胞; SH3ドメイン

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.

中性粒细胞NADPH氧化酶处于静止状态，被激活产生超氧化物，这是其他活性氧的前体，参与杀死被吞噬的细菌和炎症。NADPH氧化酶由膜整合的黄细胞色素b_<558>组成，由两个亚基gp91^<phox>和p22^<phox>组成。氧化酶的激活发生在两个胞质SH3结构域因子p47^<phox>和p67^<phox>、小的gtp结合蛋白Rac和另一个胞质因子p40^<phox>组装并转运到质膜上时。此外，细胞质因子在氧化酶激活过程中被磷酸化。组装过程是受调控的，涉及氧化酶因子之间的多种结合相互作用，导致活性氧化酶复合物。本研究证实p47^<phox>与细胞色素b_<558>、p67^<phox>与Rac、p40^<phox>与p67^<phox>之间发生特异性分子相互作用，导致氧化酶活化。

项目成果

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