Quercetin represses apolipoprotein B expression by inhibiting the transcriptional activity of C/EBPβ.

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,...

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Main Authors: Makoto Shimizu, Juan Li, Jun Inoue, Ryuichiro Sato
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4398426?pdf=render
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spelling doaj-41789352793043edb29e2707e07b96a82020-11-25T01:36:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01104e012178410.1371/journal.pone.0121784Quercetin represses apolipoprotein B expression by inhibiting the transcriptional activity of C/EBPβ.Makoto ShimizuJuan LiJun InoueRyuichiro SatoQuercetin 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.http://europepmc.org/articles/PMC4398426?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Makoto Shimizu
Juan Li
Jun Inoue
Ryuichiro Sato
spellingShingle Makoto Shimizu
Juan Li
Jun Inoue
Ryuichiro Sato
Quercetin represses apolipoprotein B expression by inhibiting the transcriptional activity of C/EBPβ.
PLoS ONE
author_facet Makoto Shimizu
Juan Li
Jun Inoue
Ryuichiro Sato
author_sort Makoto Shimizu
title Quercetin represses apolipoprotein B expression by inhibiting the transcriptional activity of C/EBPβ.
title_short Quercetin represses apolipoprotein B expression by inhibiting the transcriptional activity of C/EBPβ.
title_full Quercetin represses apolipoprotein B expression by inhibiting the transcriptional activity of C/EBPβ.
title_fullStr Quercetin represses apolipoprotein B expression by inhibiting the transcriptional activity of C/EBPβ.
title_full_unstemmed Quercetin represses apolipoprotein B expression by inhibiting the transcriptional activity of C/EBPβ.
title_sort quercetin represses apolipoprotein b expression by inhibiting the transcriptional activity of c/ebpβ.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2015-01-01
description 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.
url http://europepmc.org/articles/PMC4398426?pdf=render
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AT juanli quercetinrepressesapolipoproteinbexpressionbyinhibitingthetranscriptionalactivityofcebpb
AT juninoue quercetinrepressesapolipoproteinbexpressionbyinhibitingthetranscriptionalactivityofcebpb
AT ryuichirosato quercetinrepressesapolipoproteinbexpressionbyinhibitingthetranscriptionalactivityofcebpb
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