Regulation of expression of human intestinal bile acid-binding protein in Caco-2 cells
Regulation of expression of human intestinal bile acid-binding protein in Caco-2 cells
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DOI：
10.1042/bj3300261
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发表时间：
1998-02-15
影响因子：
4.1
通讯作者：
Fujii, H
中科院分区：
文献类型：
--
作者：
Kanda, T;Foucand, L;Fujii, H
回肠肠细胞中胆汁酸主动转运系统的分子机制仍然未知。我们研究了胆汁酸是否影响人肠上皮细胞肠胆汁酸结合蛋白（I-BABP）（该运输系统的一个组成部分）的基因表达。将分化的Caco-2细胞在人胆汁、胆汁酸或其他脂质存在下孵育。通过Northern和Western印迹分析评估I-BABP表达水平。 Caco-2 细胞在含有胆汁或胆汁酸的培养基中孵育 24 小时，导致 I-BABP mRNA 水平比对照水平显着增加 7.5 倍。胆固醇、棕榈酸、磷脂酰胆碱或考来烯胺处理的胆汁中 I-BABP mRNA 表达与对照相比均未显示任何差异。胆汁酸处理以时间和剂量依赖性方式增加 Caco-2 细胞中 I-BABP mRNA 的水平。蛋白质印迹分析表明，这种诱导导致胞质 I-BABP 增加。鹅去氧胆酸和脱氧胆酸比其他亲水性胆汁酸（包括其自身的甘氨酸缀合物）表现出更大的诱导作用，放线菌素 D 或放线菌酮预处理完全抑制胆汁酸对 I-BABP 表达的上调，胆汁酸，特别是亲脂性胆汁酸增加 Caco-2 细胞中 I-BABP 的表达，表明管腔胆汁酸在调节 I-BABP 基因表达中发挥重要作用。
Molecular mechanisms of the bile acid active transport system in the ileal enterocytes remain unknown. We examined whether bile acids affect human enterocyte gene expression of intestinal bile acid-binding protein (I-BABP), a component of this transport system. Differentiated Caco-2 cells were incubated in the presence of human bile, bile acids or other lipids, The level of I-BABP expression was evaluated by Northern and Western blot analyses. A 24 h incubation of Caco-2 cells in a medium containing either bile or bile acids resulted in a remarkable 7.5-fold increase in the I-BABP mRNA level over the control level. Neither cholesterol, palmitic acid, phosphatidylcholine nor cholestyramine treated bile showed any difference in I-BABP mRNA expression from the control. Bile acid treatment increased the level of I-BABP mRNA in Caco-2 cells in a time-and dose-dependent manner. Western blot analysis showed that this induction led to increase in cytosolic I-BABP. Chenodeoxycholic acid and deoxycholic acid showed greater induction effects than other hydrophilic bile acids, including their own glycine conjugates, Pretreatment by actinomycin D or cycloheximide completely inhibited the upregulation of I-BABP expression by bile acid, Bile acids, especially lipophilic bile acids, increase the I-BABP expression in Caco-2-cells, suggesting that luminal bile acids play an important role in regulating the I-BABP gene expression.