The Role of Oxidative Stress in the Pathogenesis of Asthma

Abstract

Oxidative stress has traditionally been considered to be a toxic byproduct of aerobic metabolism and a factor involved in tissue damage. The results of many recent studies, however, have shown that compounds involved in oxidative stress, such as H2O2, act as key molecules in signal transduction. In fact, many types of cellular stimuli, including antigens, infections, various chemical mediators, and growth factors, induce a transient increase in intracellular ROS-in particular H2O2-mainly through activation of NADPH oxidase immediately after the exposure of the stimuli to cells. 6 Furthermore, a broad field of antioxidant activity must be present within the cytosol to confine oxidative effects to the proximity of their origin and to maintain intracellular ROS levels within a narrow range. The physiologic intracellular concentration of H2O2 is 0.002-0.2 mM at steady state, reaching up to 0.5-0.7 mM when intracellular signaling is generated. What is interesting is that this physiologic concentration range appears to be consistent throughout forms of life as diverse as plants and mammals, which is unlikely to be a coincidence. 3 Many functions of intracellular negative regulators, such as various types of phosphatases and the molecules in-