Department of Diabetes, Central Clinical School, Monash University, Australia.
Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
Clin Sci (Lond). 2017 May 1;131(10):981-990. doi: 10.1042/CS20160846.
Oxidative stress is a consequence of up-regulation of pro-oxidant enzyme-induced reactive oxygen species (ROS) production and concomitant depletion of antioxidants. Elevated levels of ROS act as an intermediate and are the common denominator for various diseases including diabetes-associated macro-/micro-vascular complications and hypertension. A range of enzymes are capable of generating ROS, but the pro-oxidant enzyme family, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs), are the only enzymes known to be solely dedicated to ROS generation in the vascular tissues, kidney, aortas and eyes. While there is convincing evidence for a role of NOX1 in vascular and eye disease and for NOX4 in renal injury, the role of NOX5 in disease is less clear. Although NOX5 is highly up-regulated in humans in disease, it is absent in rodents. Thus, so far it has not been possible to study NOX5 in traditional mouse or rat models of disease. In the present review, we summarize and critically analyse the emerging evidence for a pathophysiological role of NOX5 in disease including the expression, regulation and molecular and cellular mechanisms which have been demonstrated to be involved in NOX5 activation.
氧化应激是促氧化剂诱导的活性氧（ROS）产生上调和抗氧化剂同时耗竭的结果。ROS 水平升高作为中间产物，是包括糖尿病相关的大/微血管并发症和高血压在内的各种疾病的共同特征。有一系列酶能够产生 ROS，但促氧化剂酶家族——烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶（NOXs），是唯一已知的仅在血管组织、肾脏、主动脉和眼睛中专门用于 ROS 生成的酶。虽然有令人信服的证据表明 NOX1 在血管和眼病以及 NOX4 在肾损伤中起作用，但 NOX5 在疾病中的作用尚不清楚。尽管 NOX5 在疾病中在人类中高度上调，但在啮齿动物中不存在。因此，到目前为止，还不可能在传统的小鼠或大鼠疾病模型中研究 NOX5。在本综述中，我们总结并批判性地分析了 NOX5 在疾病中的病理生理作用的新证据，包括已证明参与 NOX5 激活的表达、调节以及分子和细胞机制。
