Guichard Cécile, Pedruzzi Eric, Fay Michèle, Ben Mkaddem Sanae, Coant Nicolas, Daniel Fanny, Ogier-Denis Eric
Inserm U773, Centre de Recherche Bichat Beaujon CRB3, Université Paris 7 Denis Diderot, BP416, 46, Rue Henri Huchard, 75018 Paris, France.
Med Sci (Paris). 2006 Nov;22(11):953-9. doi: 10.1051/medsci/20062211953.
Reactive oxygen species (ROS) generated by the NADPH oxidases are conventionally thought to be cytotoxic and mutagenic and at high levels induce an oxidative stress response. The phagocyte NADPH oxidase catalyzes the NADPH-dependent reduction of molecular oxygen to generate superoxide O2-., which can dismute to generate ROS species. Together, these ROS participate in host defence by killing or damaging invading microbes. Flavocytochrome b558 is the catalytic core of the phagocyte NADPH oxidase and consists of a large glycoprotein gp91phox or Nox-2 and a small protein p22phox. The other components of the NADPH oxidase are cytosolic proteins, namely p67phox, p47phox, p40phox and Rac. A defect in any of the genes encoding gp91phox, p22phox, p67phox or p47phox results in chronic granulomatous disease, a genetic disorder characterized by severe and recurrent infections. Evidence is rapidly accumulating that low level of ROS were produced by NADPH oxidase homologs in non-phagocytic cells. To date, six human homologs (Nox-1, Nox-3, Nox-4, Nox-5, Duox-1 and Duox-2) have been recently identified in a variety of non-phagocytic cells. The identification of Nox-1 was quickly followed by the cloning of Nox-3, Nox-4, and Nox-5. In parallel, two very large members of the Nox family were discovered, namely Duox-1 and Duox-2, initially also referred to as thyroid oxidases. The physiological functions of Nox-dependent ROS generation are in progress and still require detailed characterization. Activation mechanisms and tissue distribution of the different members of the Nox family are very different, suggesting distinct physiological functions. Nox family enzymes are likely to be involved in a variety of physiological events including cell proliferation, host defence, differentiation, apoptosis, senescence and activation of growth-related signaling pathways. An increase and a decrease in the function of Nox enzymes can contribute to a wide range of pathological processes.
传统上认为，烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶产生的活性氧（ROS）具有细胞毒性和致突变性，高水平时会诱导氧化应激反应。吞噬细胞NADPH氧化酶催化NADPH依赖性的分子氧还原反应，生成超氧阴离子O2-，O2-可歧化生成ROS。这些ROS共同通过杀死或损伤入侵微生物参与宿主防御。黄素细胞色素b558是吞噬细胞NADPH氧化酶的催化核心，由一个大的糖蛋白gp91phox或Nox-2和一个小蛋白p22phox组成。NADPH氧化酶的其他成分是胞质蛋白，即p67phox、p47phox、p40phox和Rac。编码gp91phox、p22phox、p67phox或p47phox的任何一个基因出现缺陷都会导致慢性肉芽肿病，这是一种以严重且反复感染为特征的遗传性疾病。越来越多的证据表明，非吞噬细胞中的NADPH氧化酶同系物会产生低水平的ROS。迄今为止，最近已在多种非吞噬细胞中鉴定出六种人类同系物（Nox-1、Nox-3、Nox-4、Nox-5、双氧化酶-1和双氧化酶-2）。在鉴定出Nox-1之后，很快又克隆出了Nox-3、Nox-4和Nox-5。与此同时，发现了Nox家族的两个非常大的成员，即双氧化酶-1和双氧化酶-2，最初它们也被称为甲状腺氧化酶。Nox依赖性ROS生成的生理功能正在研究中，仍需要详细表征。Nox家族不同成员的激活机制和组织分布差异很大，这表明它们具有不同的生理功能。Nox家族酶可能参与多种生理事件，包括细胞增殖、宿主防御、分化、凋亡、衰老以及生长相关信号通路的激活。Nox酶功能的增加和减少都可能导致广泛的病理过程。
