Physiological roles of NOX/NADPH oxidase, the superoxide-generating enzyme

NADPH oxidase is a superoxide (O-2(center dot-))-generating enzyme first identified in phagocytes, essential for their bactericidal activities. Later, in non-phagocytes, production of O-2(center dot-) was also demonstrated in an NADPH-dependent manner. In the last decade, several non-phagocyte-type NADPH oxidases have been identified. The catalytic subunit of these oxidases, NOX, constitutes the NOX family. There are five homologs in the family, NOX1 to NOX5, and two related enzymes, DUOX1 and DUOX2. Transgenic or gene-disrupted mice of the NOX family have also been established. NOX/DUOX proteins possess distinct features in the dependency on other components for their enzymatic activities, tissue distributions, and physiological functions. This review summarized the characteristics of the NOX family proteins, especially focused on their functions clarified through studies using gene-modified mice.