Nox/Duox Family of NADPH Oxidases: Lessons from Knockout Mouse Models

Abstract

Nox/Duox NADPH oxidases are now considered the primary, regulated sources of reactive oxygen species (ROS). These enzymes are expressed in diverse cells and tissues, and their products are essential in several physiological settings. Knockout mouse models are instrumental in identifying the physiological functions of Nox/Duox enzymes as well as in exploring the impact of their pharmacological targeting on disease progression. The currently available data from experiments on knockout animals suggest that the lack of non-phagocytic Nox/Duox enzymes often modifies the course and phenotype in many disease models. Nevertheless, as illustrated by studies on Nox4-deficient animals, the absence of Nox-derived ROS can also lead to aggravated disease manifestation, reinforcing the need for a more balanced view on the role of ROS in health and disease. Members of the Nox/Duox NADPH oxidase family produce ROS in a regulated manner in several different cells and tissues.Pharmacological inhibition of non-phagocytic Nox/Duox enzymes might have therapeutic potential.Several studies have described the disease-modifying phenotypes of Nox1 and Nox4 knockouts.The lack of Nox4-derived ROS can lead to aggravated disease development, which is in contrast to the prevailing dogma that considers ROS to be generally harmful. © 2016 Elsevier Ltd.