Hypoxia and Reactive Oxygen Species

Abstract

In recent years, superoxide and other reactive oxygen species (ROS) have been acknowledged to act not only as unwanted and even toxic byproducts of aerobic metabolism but also as important signaling molecules in various physiological and pathophysiological conditions. This has broadened the field of oxygen signaling in a substantial way given the fact that superoxide is derived from molecular oxygen. In this regard ROS and ROS-dependent signaling pathways appear to be connected in different ways to the pathways involved in the adaptation towards a low-oxygen environment.One of the major pathways regulated by oxygen availability relies on the activity of hypoxia-inducible transcription factors (HIFs). Originally described to be only induced and activated under hypoxia, accumulating evidence suggests that HIFs play a more general role in response to diverse cellular activators and stressors, many of which use ROS as signal transducers. On the other hand, the HIF pathway has also been implicated in controlling some important ROS-generating systems. Thus, an important cross talk exists between ROS signaling systems and the HIF pathway which may have substantial consequences for the pathogenesis of various disorders including cancer.