title: Analysis of flavonoids regulating the expression of UGT1A1 via xenobiotic receptors in intestinal epithelial cells.
abstract: UDP-glucuronosyltransferase (UGT) 1A1 is one of the major metabolic enzymes for the detoxification of harmful xenobiotics in intestines, and its expression is regulated by transcription factors like the aryl hydrocarbon receptor (AhR) and the pregnane X receptor (PXR). A screening assay using real-time PCR showed that baicalein and 3-hydroxyflavone induced human UGT1A1 mRNA expression in LS180 cells. Experimental results confirmed that these flavonoids increased UGT1A protein expression as well as its enzymatic activity. The results indicated that baicalein and 3-hydroxyflavone increased the transcriptional activity of UGT1A1 via AhR and PXR, respectively. Observation via immunofluorescence microscopy suggested that baicalein and 3-hydroxyflavone further induced nuclear translocation of AhR and PXR, respectively. In addition, direct interaction between baicalein and AhR or 3-hydroxyflavone and PXR were observed using the quartz crystal microbalance method. These results elucidate the molecular mechanism of flavonoid-induced UGT1A1 gene expression via xenobiotic receptors in the intestines.
authors.affiliation: Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan.
authors.forename: Yuto
authors.initials: Y
authors.lastname: Hiura
authors.forename: Hideo
authors.initials: H
authors.lastname: Satsu
authors.forename: Mika
authors.initials: M
authors.lastname: Hamada
authors.forename: Makoto
authors.initials: M
authors.lastname: Shimizu
mesh_terms: D021581:Active Transport, Cell Nucleus; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology*; D044950:Flavanones / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D014453:Glucuronosyltransferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology; D058525:Quartz Crystal Microbalance Techniques; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D015262:Xenobiotics / Q000378:metabolism; D000099148:UGT1A1 Enzyme
chemical_list: D044950:Flavanones; D005419:Flavonoids; D014453:Glucuronosyltransferase; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D015262:Xenobiotics; D000099148:UGT1A1 Enzyme; C006680:baicalein; C041477:3-hydroxyflavone
keywords: 3-hydroxyflavone; UGT1A1; aryl hydrocarbon receptor; baicalein; pregnane X receptor; quartz crystal microbalance