Guo Shuhui, Chen Xiuping
a State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Macao , China.
J Drug Target. 2015 Dec;23(10):888-96. doi: 10.3109/1061186X.2015.1036276. Epub 2015 May 7.
Increased generation of reactive oxygen species (ROS) has been implicated in the pathogenesis of a variety of diseases such as cardiovascular diseases and cancer. NADPH oxidase (Nox), a multicomponent enzyme, has been identified as one of the key sources of ROS. Nox4, one of the seven members of Nox family (Nox1, Nox2, Nox3, Nox4, Nox5, Duox1 and Duox2), has been extensively investigated in recent years. Its unique structures result in the constitutive generation of hydrogen peroxide (H2O2) as the main product. As a key oxygen sensor, Nox4-derived H2O2 plays diverse roles in cell proliferation, migration and death. Increased expression of Nox4 in cancer has been observed, which participates in metastasis, angiogenesis and apoptosis. Expression of Nox4 in endothelial cells actively mediated endothelial activation, dysfunction and injury, which contributes to the development of atherosclerosis, hypertension, cardiac hypertrophy and among others. This article explores the experimental studies related to the gene, structure, physiological function and pathological significance of Nox4. As Nox4 might serve as a potential target for the therapy of cardiovascular diseases and cancer, the Nox4 inhibitor is also discussed in this article.
活性氧（ROS）生成增加与多种疾病（如心血管疾病和癌症）的发病机制有关。NADPH氧化酶（Nox）是一种多组分酶，已被确定为ROS的主要来源之一。Nox4是Nox家族七个成员（Nox1、Nox2、Nox3、Nox4、Nox5、Duox1和Duox2）之一，近年来受到广泛研究。其独特的结构导致以过氧化氢（H2O2）作为主要产物的组成型生成。作为关键的氧传感器，Nox4衍生的H2O2在细胞增殖、迁移和死亡中发挥多种作用。已观察到Nox4在癌症中的表达增加，其参与转移、血管生成和凋亡。Nox4在内皮细胞中的表达积极介导内皮细胞活化、功能障碍和损伤，这有助于动脉粥样硬化、高血压、心脏肥大等疾病的发展。本文探讨了与Nox4的基因、结构、生理功能和病理意义相关的实验研究。由于Nox4可能作为心血管疾病和癌症治疗的潜在靶点，本文还讨论了Nox4抑制剂。
