Khan Wahid Ali, Ali Khan Mohd Wajid
Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha, KSA.
Curr Drug Metab. 2015;17(1):65-74. doi: 10.2174/1389200216666151103115210.
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.
细胞色素P450酶负责I相代谢途径中各种内源性雌激素的羟基化。细胞色素P450产生具有激素活性的雌激素代谢物，这些代谢物通常具有反应性和致突变性。虽然已知这些代谢物在自身免疫中起重要作用，但其潜在机制仍不清楚。在此我们报告，细胞色素P450介导的雌激素代谢物会产生高浓度的活性氧（ROS），从而导致DNA损伤。这种DNA损伤会改变其免疫原性，导致自身抗体浓度的诱导和升高，进而引发各种自身免疫性疾病。在此我们重点关注细胞色素P450催化的雌激素代谢物诱导免疫反应并随后产生自身免疫现象的机制。
