Oxidative stress responses--what have genome-scale studies taught us?

Abstract

Oxidative stress arises from an imbalance between generation and elimination of reactive oxygen species, often leading to cell death. Genomic tools are expanding our understanding of the antioxidant defenses aerobes have evolved and the recently discovered role(s) of reactive oxygen species in signaling.

Figure 1

Oxidative stress results from imbalance between the levels of reactive oxygen species (ROS) and antioxidants (AOX). Under normal circumstances, cells are able to balance the production of oxidants and antioxidants (such as catalase and superoxide dismutase), resulting in redox equilibrium. Oxidative stress occurs when cells are subjected to excess levels of ROS, or as a result of depletion in antioxidant defenses.

Figure 2

Some of the pleiotropic effects of ROS. They have many roles as signaling molecules in addition to their scavenging protective functions in biological systems.

Figure 3

The major signaling pathways activated in response to oxidative stress. ROS can originate from metabolic activity or from external environmental signals and are modulated by antioxidants to nontoxic levels at which point they serve as signaling molecules. ROS can activate gene transcription in two ways: either via transcription factors (such as, NFκB, AP-1 and ARE-binding proteins, ARE-BP) that can interact directly with specific DNA motifs, including ARE, on promoters of target genes; or via activation of MAP kinase cascades, which in turn activate transcription factors that trigger target gene transcription. The degree to which a given pathway is activated is dependent on the nature and duration of the stress, as well as on cell type and developmental stage.