Title:Cytochrome P450-Mediated Estrogen Metabolites and Autoimmunity: Relationship and Link to Free Radicals
Volume: 17
Issue: 1
Author(s): Wahid Ali Khan and Mohd. Wajid Ali Khan
Affiliation:
Keywords:
2-hydroxyestradiol, 4-Hydroxyestradiol, autoimmunity, cytochromeP450, DNA, estrogen metabolites, ROS.
Abstract: Cytochrome P450 enzymes are responsible for the hydroxylation of various endogenous estrogens of the
Phase I metabolic pathway. Cytochrome P450s produce hormonally active estrogen metabolites that are typically
reactive and mutagenic. Although these metabolites are known to have important roles in autoimmunity, the underlying
mechanism of this remains unknown. Here we report that cytochrome P450-mediated estrogen metabolites
produce high ROS concentrations that can result in DNA damage. Such DNA damage can alter its immunogenicity,
resulting in the induction and elevation of autoantibody concentrations, thus generating various autoimmune
conditions. Here we focus on the mechanisms through which cytochrome P450-catalyzed estrogen metabolites induce
immune responses and subsequently produce the autoimmune phenomenon.
