Induction of Cytochrome P450 Enzymes

Abstract

Over the last decade, great strides have been made in understanding the roles that the nuclear receptors PXR, CAR, PPARα, and AHR play in the induction of CYP genes. The ability of xenobiotics to bind and activate NRs to induce the expression of the CYP enzymes involved in their metabolism provides a mechanism by which an organism can mount an adaptive response to its changing chemical environment. The identification of endogenous ligands for some NRs indicates that these receptors play important roles in regulating CYP levels during physiological processes as well. It has become clear that the expression of many CYP genes is dependent on more than one NR. Recent studies have demonstrated that NRs often share xenobiotic ligands, response elements, and target CYP genes. The existence of multiple xenobiotic receptors with broad and sometimes overlapping functions likely increases the ability of an organism to detect and respond to a wide range of chemicals. The challenge for the future will be to understand how the NRs participate in a complex network to regulate CYP gene expression and to mediate the physiological response to xenobiotics.