title: Quercetin represses apolipoprotein B expression by inhibiting the transcriptional activity of C/EBPβ.
abstract: Quercetin is one of the most abundant polyphenolic flavonoids found in fruits and vegetables and has anti-oxidative and anti-obesity effects. Because the small intestine is a major absorptive organ of dietary nutrients, it is likely that highly concentrated food constituents, including polyphenols, are present in the small intestinal epithelial cells, suggesting that food factors may have a profound effect in this tissue. To identify novel targets of quercetin in the intestinal enterocytes, mRNA profiling using human intestinal epithelial Caco-2 cells was performed. We found that mRNA levels of some apolipoproteins, particularly apolipoprotein B (apoB), are downregulated in the presence of quercetin. On the exposure of Caco-2 cells to quercetin, both mRNA and protein levels of apoB were decreased. Promoter analysis of the human apoB revealed that quercetin response element is localized at the 5'-proximal promoter region, which contains a conserved CCAAT enhancer-binding protein (C/EBP)-response element. We found that quercetin reduces the promoter activity of apoB, driven by the enforced expression of C/EBPβ. Quercetin had no effect on either mRNA or protein levels of C/EBPβ. In contrast, we found that quercetin inhibits the transcriptional activity of C/EBPβ but not its recruitment to the apoB promoter. On the exposure of Caco-2 cells to quercetin 3-O-glucuronide, which is in a cell-impermeable form, no notable change in apoB mRNA was observed, suggesting an intracellular action of quercetin. In vitro interaction experiments using quercetin-conjugated beads revealed that quercetin binds to C/EBPβ. Our results describe a novel regulatory mechanism of transcription of apolipoprotein genes by quercetin in the intestinal enterocytes.
authors: Department of Applied Biological Chemistry, The University of Tokyo 1-1-1 Yayoi, Bunkyo, Tokyo, Japan.
authors: Makoto
authors: M
authors: Shimizu
authors: Department of Applied Biological Chemistry, The University of Tokyo 1-1-1 Yayoi, Bunkyo, Tokyo, Japan.
authors: Juan
authors: J
authors: Li
authors: Department of Applied Biological Chemistry, The University of Tokyo 1-1-1 Yayoi, Bunkyo, Tokyo, Japan.
authors: Jun
authors: J
authors: Inoue
authors: Department of Applied Biological Chemistry, The University of Tokyo 1-1-1 Yayoi, Bunkyo, Tokyo, Japan.
authors: Ryuichiro
authors: R
authors: Sato
mesh_terms: D001055:Apolipoproteins B / Q000096:biosynthesis* / Q000235:genetics; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000096:biosynthesis* / Q000235:genetics; D018938:Caco-2 Cells; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D011401:Promoter Regions, Genetic; D011794:Quercetin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D001055:Apolipoproteins B; D022782:CCAAT-Enhancer-Binding Protein-beta; D012333:RNA, Messenger; D011794:Quercetin