<br>NADPH 氧化酶 (NOX)：从发现、分子机制到生理学和病理学的概述,Antioxidants

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NADPH 氧化酶 (NOX)：从发现、分子机制到生理学和病理学的概述
Antioxidants ( IF 6.0 ) Pub Date : 2021-06-01 , DOI: 10.3390/antiox10060890
Annelise Vermot ₁ , Isabelle Petit-Härtlein ₁ , Susan M E Smith ₂ , Franck Fieschi ₁

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产生活性氧 (ROS) 的酶 NADPH 氧化酶 (NOX) 首次在吞噬细胞膜中被发现。多年来，它唯一已知的作用是在免疫防御中，它产生的活性氧导致免疫细胞消灭病原体。来自吞噬细胞的 NOX 通过单电子跨膜转移到分子氧来催化超氧阴离子的产生。多年来，人们发现了吞噬细胞 NADPH 氧化酶催化亚基的六种人类同源物：NOX1、NOX3、NOX4、NOX5、DUOX1 和 DUOX2。与吞噬细胞 NADPH 氧化酶组装体本身中存在的 NOX2/gp91 ^phox成分一起，同源物现在被称为 NADPH 氧化酶的 NOX 家族。 NOX 是复杂的多结构域蛋白质，对于与其他蛋白质组合组装以获得活性具有不同的要求。最近对原核和真核 NOX 的结构见解为理解 NOX 调节和 ROS 产生（超氧化物或过氧化氢）固有的分子机制开辟了新的视角。这种新的结构信息肯定将为人类疾病的新研究提供信息。作为专门的 ROS 生产者，NOX 酶参与许多重要的生理过程，包括宿主防御、蛋白质翻译后加工、细胞信号传导、基因表达调节和细胞分化。本综述将讨论这些生理背景的多样性。我们还讨论了 NOX 失调，它可能导致多种严重病理，如动脉粥样硬化、高血压、糖尿病肾病、肺纤维化、癌症或神经退行性疾病，使该膜蛋白家族具有强烈的治疗意义。

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NADPH Oxidases (NOX): An Overview from Discovery, Molecular Mechanisms to Physiology and Pathology

The reactive oxygen species (ROS)-producing enzyme NADPH oxidase (NOX) was first identified in the membrane of phagocytic cells. For many years, its only known role was in immune defense, where its ROS production leads to the destruction of pathogens by the immune cells. NOX from phagocytes catalyzes, via one-electron trans-membrane transfer to molecular oxygen, the production of the superoxide anion. Over the years, six human homologs of the catalytic subunit of the phagocyte NADPH oxidase were found: NOX1, NOX3, NOX4, NOX5, DUOX1, and DUOX2. Together with the NOX2/gp91^phox component present in the phagocyte NADPH oxidase assembly itself, the homologs are now referred to as the NOX family of NADPH oxidases. NOX are complex multidomain proteins with varying requirements for assembly with combinations of other proteins for activity. The recent structural insights acquired on both prokaryotic and eukaryotic NOX open new perspectives for the understanding of the molecular mechanisms inherent to NOX regulation and ROS production (superoxide or hydrogen peroxide). This new structural information will certainly inform new investigations of human disease. As specialized ROS producers, NOX enzymes participate in numerous crucial physiological processes, including host defense, the post-translational processing of proteins, cellular signaling, regulation of gene expression, and cell differentiation. These diversities of physiological context will be discussed in this review. We also discuss NOX misregulation, which can contribute to a wide range of severe pathologies, such as atherosclerosis, hypertension, diabetic nephropathy, lung fibrosis, cancer, or neurodegenerative diseases, giving this family of membrane proteins a strong therapeutic interest.

更新日期：2021-06-01

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