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中性粒细胞和其他哺乳动物细胞的NADPH氧化酶对超氧化物生成的调节。

The regulation of superoxide production by the NADPH oxidase of neutrophils and other mammalian cells.

作者信息

Jones O T

机构信息

Department of Biochemistry, School of Medical Sciences, University of Bristol, UK.

出版信息

Bioessays. 1994 Dec;16(12):919-23. doi: 10.1002/bies.950161211.

DOI:10.1002/bies.950161211
PMID:7840772
Abstract

Superoxide is produced by a NADPH oxidase of phagocytic cells and contributes to their microbicidal activities. The oxidase is activated when receptors in the neutrophil plasma membrane bind to the target microbe. These receptors recognise antibodies and complement fragments which coat the target cell. The oxidase electron transport chain, located in the plasma membrane, comprises a low potential cytochrome b heterodimer (gp 91-phox and p22-phox) associated with FAD. It is non-functional until at least three proteins, p67-phox, p47-phox and p21rac (and possibly others), move from the cytosol to dock on the cytochrome b. The docking involves the interaction of SH3 domains on p47-phox or p67-phox with a proline-rich sequence on the small subunit of the cytochrome b. These SH3 domains may become exposed following phosphorylation of p47-phox by protein kinase C or, in model systems, by addition of arachidonic acid to reconstitution mixtures. Following the docking process the electron-transporting component is able to transfer electrons from NADPH to oxygen. This electrogenic event is charge-compensated by the opening of a proton channel. Components of the oxidase are expressed in non-phagocytes, where their function is uncertain but could be related to some signal function of superoxide.

摘要

超氧化物由吞噬细胞的NADPH氧化酶产生,并有助于其杀菌活性。当中性粒细胞膜中的受体与靶微生物结合时,该氧化酶被激活。这些受体识别包被靶细胞的抗体和补体片段。位于质膜中的氧化酶电子传递链由与FAD相关的低电位细胞色素b异二聚体(gp 91-phox和p22-phox)组成。在至少三种蛋白质p67-phox、p47-phox和p21rac(可能还有其他蛋白质)从胞质溶胶移动到细胞色素b上停靠之前,它是无功能的。停靠涉及p47-phox或p67-phox上的SH3结构域与细胞色素b小亚基上富含脯氨酸的序列之间的相互作用。这些SH3结构域可能在蛋白激酶C使p47-phox磷酸化后暴露,或者在模型系统中,通过向重构混合物中添加花生四烯酸而暴露。在停靠过程之后,电子传递成分能够将电子从NADPH转移到氧气。这种产电事件通过质子通道的开放进行电荷补偿。氧化酶的成分在非吞噬细胞中表达,其功能尚不确定,但可能与超氧化物的某些信号功能有关。

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