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.
Keywords: 2-hydroxyestradiol, 4-Hydroxyestradiol, autoimmunity, cytochromeP450, DNA, estrogen metabolites, ROS.
Current Drug Metabolism
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.
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Cite this article as:
Khan Ali Wahid and Ali Khan Wajid Mohd., Cytochrome P450-Mediated Estrogen Metabolites and Autoimmunity: Relationship and Link to Free Radicals, Current Drug Metabolism 2016; 17 (1) . https://dx.doi.org/10.2174/1389200216666151103115210
DOI https://dx.doi.org/10.2174/1389200216666151103115210 |
Print ISSN 1389-2002 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5453 |
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