Activity of NAD(P)H oxidase in relation to genotypes: Comprehensive genetic mapping of single nucleotide polymorphisms (SNPs) in the p22~(phox) subunit

摘要

Reactive oxygen species (ROS) play a major role in carcinogenesis but also in the mechanisms of action of radiotherapy and chemotherapy of malignancies. The NAD(P)H-oxidase catalyzes the NAD(P)H-dependent reduction of molecular oxygen (O_2) to superoxide (O_2) from which other aggressive ROS are generated. Among many different functions, ROS play a pivotal role in the defense against microorganisms and in signal transduction. Members of the NAD(P)H oxidase family are present in almost all cell types, however the most common is N0X2 which is highly expressed in phagocytic cells. After stimulation, the regulatory cytosolic components of N0X2 (p40~Phox, p47~Phox, p67~Phox, rac2) are translocated to the membrane-anchored sub-units gp91Phox and p22~Phox. The big gp9l~Phox subunit forms the catalytic core of the enzyme and p22~Phox is a smaller stabilizing protein. The assembly of all subunits results in the generation of superoxide