Mammalian NADPH Oxidases
Mammalian NADPH Oxidases
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DOI：
10.1007/978-1-4939-9424-3_2
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发表时间：
2019-01-01
期刊：
影响因子：
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通讯作者：
Krause, Karl-Heinz
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文献类型：
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作者：
Buvelot, Helene;Jaquet, Vincent;Krause, Karl-Heinz
活性氧（ROS）是一种高活性的氧衍生物。最初，它们被认为是代谢副产物（尤其是线粒体），不断导致衰老和疾病。然而，在过去的几十年里，越来越明显的是，几乎所有真核细胞都具有特异性的ros产生酶，即NOX NADPH氧化酶。在大多数哺乳动物中，有七种氮氧化物异构体：三个密切相关的异构体，NOX1, 2, 3，它们被细胞质亚基激活；NOX4，似乎具有组成活性；以及含有ef -hand的Ca2+激活亚型NOX5和DUOX1和2。氮氧化物基因的功能丧失突变可导致严重的人类疾病。NOX2缺乏导致原发性免疫缺陷，而DUOX2缺乏表现为先天性甲状腺功能减退。缺氧小鼠为探索各种NADPH氧化酶的生理功能提供了重要的工具，因为Nox2， Nox3和Duox2的功能丧失会导致自发表型。Nox1、Nox4和Duox1的基因缺失不会导致明显的小鼠表型（NOX5基因在啮齿动物中缺失，因此不能使用敲除小鼠进行研究）。自从在世纪之交发现氮氧化物家族以来，在了解氮氧化物的生物化学和生理学方面取得了很大进展；然而，迄今仍有许多问题没有得到解答。本章概述了我们目前对哺乳动物NOX/DUOX酶的了解。
Reactive oxygen species (ROS) are highly reactive oxygen derivatives. Initially, they were considered as metabolic by-products (of mitochondria in particular), which consistently lead to aging and disease. Over the last decades, however, it became increasingly apparent that virtually all eukaryotic cells possess specifically ROS-producing enzymes, namely, NOX NADPH oxidases. In most mammals, there are seven NOX isoforms: three closely related isoforms, NOX1, 2, 3, which are activated by cytoplasmic subunits; NOX4, which appears to be constitutively active; and the EF-hand-containing Ca2+-activated isoforms NOX5 and DUOX1 and 2. Loss-of-function mutations in NOX genes can lead to serious human disease. NOX2 deficiency leads to primary immune deficiency, while DUOX2 deficiency presents as congenital hypothyroidism. Nox-deficient mice provide important tools to explore the physiological functions of various NADPH oxidases as a loss of function in Nox2, Nox3, and Duox2 leads to a spontaneous phenotype. The genetic absence of Nox1, Nox4, and Duox1 does not result in an obvious mouse phenotype (the NOX5 gene is absent in rodents and can therefore not be studied using knockout mice). Since the discovery of the NOX family at the turn of the millennium, much progress in understanding the biochemistry and the physiology of NOX has been made; however many questions remain unanswered to date. This chapter is an overview of our present knowledge on mammalian NOX/DUOX enzymes.