Quercetin represses apolipoprotein B expression by inhibiting the transcriptional activity of C/EBPβ.
Quercetin represses apolipoprotein B expression by inhibiting the transcriptional activity of C/EBPβ.
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DOI：
10.1371/journal.pone.0121784
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Sato R
中科院分区：
文献类型：
--
作者：
Shimizu M;Li J;Inoue J;Sato R
槲皮素是水果和蔬菜中最丰富的多酚类黄酮之一，具有抗氧化和抗肥胖作用。由于小肠是膳食营养素的主要吸收器官，因此很可能高度浓缩的食物成分，包括多酚，存在于小肠上皮细胞中，这表明食物因素可能对该组织产生深远的影响。为了鉴定槲皮素在肠上皮细胞中的新靶点，使用人肠上皮Caco-2细胞进行mRNA谱分析。我们发现，在槲皮素的存在下，一些载脂蛋白，特别是载脂蛋白B（apo B）的mRNA水平下调。槲皮素作用于Caco-2细胞后，apoB的mRNA和蛋白水平均下降。对人apoB启动子的分析表明，槲皮素反应元件位于apoB启动子的5′端，其中含有一个保守的CCAAT增强子结合蛋白（C/EBP）反应元件。我们发现槲皮素降低了apoB的启动子活性，这是由C/EBPβ的强制表达驱动的。槲皮素对C/EBPβ的mRNA或蛋白水平均无影响。相反，我们发现槲皮素抑制C/EBPβ的转录活性，但不抑制其向apoB启动子的募集。在Caco-2细胞暴露于槲皮素3-O-葡糖苷酸（细胞不可渗透形式）时，未观察到apoB mRNA的显著变化，表明槲皮素具有细胞内作用。使用槲皮素缀合珠的体外相互作用实验显示，槲皮素与C/EBPβ结合。我们的研究结果描述了一种新的调控机制，载脂蛋白基因的转录槲皮素在肠上皮细胞。
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.
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DOI：
10.1016/j.bbrc.2008.06.077
发表时间：
2008-09-05
影响因子：
3.1
作者：
Ahn, Jiyun;Lee, Hyunjung;Ha, Taleyoul
通讯作者：
Ha, Taleyoul
影响因子：
4.8
作者：
Sever, N;Song, BL;DeBose-Boyd, RA
通讯作者：
DeBose-Boyd, RA
影响因子：
6.1
作者：
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通讯作者：
Naseem, Imrana
影响因子：
64.5
作者：
Bookout, Angie L.;Jeong, Yangsik;Mangelsdorf, David J.
通讯作者：
Mangelsdorf, David J.
影响因子：
4.8
作者：
Iqbal, Jahangir;Parks, John S.;Hussain, M. Mahmood
通讯作者：
Hussain, M. Mahmood