Farnesoid X Receptor Agonist Represses Cytochrome P450 2D6 Expression by Upregulating Small Heterodimer Partner.
Animals; Cytochrome P-450 CYP2D6/*biosynthesis; Cytochrome P-450 Enzyme Inhibitors/*pharmacology; Cytoplasmic and Nuclear/*agonists; Enzymologic/drug effects; Gene Expression Regulation; Genetic/drug effects/genetics; HEK293 Cells; Hepatocytes/drug effects/enzymology/metabolism; Humans; Isoxazoles/*pharmacology; Knockout; Mice; Receptors; Transcription; Transgenic
Cytochrome P450 2D6 (CYP2D6) is a major drug-metabolizing enzyme responsible for eliminating approximately 20% of marketed drugs. Studies have shown that differential transcriptional regulation of CYP2D6 may contribute to large interindividual variability in CYP2D6-mediated drug metabolism. However, the factors governing CYP2D6 transcription are largely unknown. We previously demonstrated small heterodimer partner (SHP) as a novel transcriptional repressor of CYP2D6 expression. SHP is a representative target gene of the farnesoid X receptor (FXR). The objective of this study is to investigate whether an agonist of FXR,
Pan Xian; Lee Yoon-Kwang; Jeong Hyunyoung
Drug metabolism and disposition: the biological fate of chemicals
2015
2015-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1124/dmd.115.064758" target="_blank" rel="noreferrer noopener">10.1124/dmd.115.064758</a>
Selective Targeting of Heme Protein in Cytochrome P450 and Nitric Oxide Synthase by Diphenyleneiodonium.
*cytochrome P450; *flavoenzymes; *heme; *nitric oxide synthase; *reactive oxygen species; Animals; Cytochrome P-450 Enzyme Inhibitors/*pharmacology; Cytochrome P-450 Enzyme System/*metabolism; Dose-Response Relationship; Drug; Heme/*antagonists & inhibitors/metabolism; Humans; Liver/drug effects/enzymology; Mice; Microsomes; Nitric Oxide Synthase Type II/*antagonists & inhibitors/metabolism; Nitric Oxide/metabolism; Onium Compounds/*pharmacology; Rats; Recombinant Proteins/metabolism; Sprague-Dawley; Time Factors
Cytochrome P450 (CYP) enzymes mediate mixed-function oxidation reactions important in drug metabolism. The aromatic heterocyclic cation, diphenyleneiodonium (DPI), binds flavin in cytochrome P450 reductase and inhibits
Szilagyi John T; Mishin Vladimir; Heck Diane E; Jan Yi-Hua; Aleksunes Lauren M; Richardson Jason R; Heindel Ned D; Laskin Debra L; Laskin Jeffrey D
Toxicological sciences : an official journal of the Society of Toxicology
2016
2016-05
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1093/toxsci/kfw031" target="_blank" rel="noreferrer noopener">10.1093/toxsci/kfw031</a>