Novel sources of reactive oxygen species in the human body

Abstract

There are several sources of reactive oxygen in the human body. Production of superoxide in mitochondria is a by-product of the function of the respiratory chain [1]. The first known example of regulated generation of reactive oxygen species (ROS) in mammalian cells was through the respiratory burst of phagocytic cells by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. This enzyme complex uses electrons derived from intracellular NADPH to generate superoxide anion, which is further processed to form hydrogen peroxide and other ROS-providing host defense against bacterial and fungal pathogens [2]. The essential role of the phagocytic oxidase in host defense is well illustrated by the serious phenotype of chronic granulomatous disease (CGD), in which susceptibility to infections develops in the absence of a functional phagocytic oxidase [3]. Non-mitochondrial production of ROS was detected in various cell types, showing that intentional generation of ROS is a general feature of many tissues, rather than a unique function of phagocytes. Homology searches in human genome databases resulted in the discovery of six novel NADPH oxidase enzymes: Nox1, Nox3, Nox4, Nox5, Duox1 and Duox2 [4–6]. They all have at least partially similar structure and generate ROS in response to various stimuli. The physiological function of these proteins and their potential role in the pathogenesis of human diseases is currently under intensive investigation. Structural aspects