Aryl Hydrocarbon Receptor in Oxidative Stress as a Double Agent and Its Biological and Therapeutic Significance

Abstract

The aryl hydrocarbon receptor (AhR) has long been implicated in the induction of a battery of genes involved in the metabolism of xenobiotics and endogenous compounds. AhR is a ligand-activated transcription factor necessary for the launch of transcriptional responses important in health and disease. In past decades, evidence has accumulated that AhR is associated with the cellular response to oxidative stress, and this property of AhR must be taken into account during investigations into a mechanism of action of xenobiotics that is able to activate AhR or that is susceptible to metabolic activation by enzymes encoded by the genes that are under the control of AhR. In this review, we examine various mechanisms by which AhR takes part in the oxidative-stress response, including antioxidant and prooxidant enzymes and cytochrome P450. We also show that AhR, as a participant in the redox balance and as a modulator of redox signals, is being increasingly studied as a target for a new class of therapeutic compounds and as an explanation for the pathogenesis of some disorders.

Keywords

• reactive oxygen species
• oxidative stress
• antioxidant
• aryl hydrocarbon receptor
• AhR
• nuclear factor-erythroid 2-related factor 2