Carotenoid transport is decreased and expression of the lipid transporters SR-BI, NPC1L1, and ABCA1 is downregulated in Caco-2 cells treated with ezetimibe
Carotenoid transport is decreased and expression of the lipid transporters SR-BI, NPC1L1, and ABCA1 is downregulated in Caco-2 cells treated with ezetimibe
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DOI：
10.1093/jn/135.10.2305
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发表时间：
2005-10-01
影响因子：
4.2
通讯作者：
Harrison, Earl H.
中科院分区：
文献类型：
--
作者：
During, Alexandrine;Dawson, Harry D.;Harrison, Earl H.
数据表明，肠道类胡萝卜素的吸收是一个促进的过程。本研究旨在确定类胡萝卜素和胆固醇是否具有共同的肠道吸收途径（转运蛋白）。将膜上的分化Caco-2细胞与类胡萝卜素（1 μ mol/L）一起孵育（16小时），其中有或没有依折麦布（EZ; Zetiae（R），胆固醇转运抑制剂），以及有或没有针对受体簇决定簇36（CD 36）和清道夫受体B类I型（SR-BI）的抗体。EZ（10 mg/L）降低Caco-2细胞中的类胡萝卜素转运（细胞摄取+分泌）如下：β-胡萝卜素近似于α-胡萝卜素（50%抑制）>> β-隐黄质近似于番茄红素（20%）>>叶黄素：玉米黄质（1：1）（7%）。EZ降低胆固醇转运31%，但不降低视黄醇转运。β-胡萝卜素转运也被抗SR-B1抑制，但不被抗CD 36抑制。EZ和抗SR-BI对β-胡萝卜素转运的抑制作用是相加的，表明它们可能具有不同的靶点。最后，用EZ处理的分化的Caco-2细胞显示表面受体SR-BI、尼曼-匹克型C1样1蛋白（NPC 1 L1）和ATP结合盒转运蛋白亚家族A（ABCA 1）以及核受体类视黄酸受体（RAR）γ、固醇调节元件结合蛋白（SREBP）-1和-2的mRNA表达显著降低，和肝X受体（LXR）β，如通过实时PCR分析评估的。数据表明，1）EZ是类胡萝卜素转运的抑制剂，这种作用随着类胡萝卜素分子极性的增加而降低，2）SR-BI参与类胡萝卜素转运，3）EZ不仅可以通过与胆固醇转运蛋白的物理相互作用发挥作用，还可以通过下调这些蛋白质的表达发挥作用。细胞对类胡萝卜素的吸收和流出，像胆固醇一样，可能涉及一种以上的转运蛋白。
Data suggest that intestinal carotenoid absorption is a facilitated process. The present study was conducted to determine whether carotenoids and cholesterol share common pathways (transporters) for their intestinal absorption. Differentiated Caco-2 cells on membranes were incubated (16 h) with a carotenoid (1 mu mol/L) with or without ezetimibe (EZ; Zetiae (R), an inhibitor of cholesterol transport), and with or without antibodies against the receptors, cluster determinant 36 (CD36) and scavenger receptor class B, type I (SR-BI). Carotenoid transport in Caco-2 cells (cellular uptake + secretion) was decreased by EZ (10 mg/L) as follows: beta-carotene approximate to alpha-carotene (50% inhibition) >> beta-cryptoxanthin approximate to lycopene (20%) >> lutein:zeaxanthin (1:1) (7%). EZ reduced cholesterol transport by 31 %, but not retinol transport. beta-Carotene transport was also inhibited by anti-SR-Bl, but not by anti-CD36. The inhibitory effects of EZ and anti-SR-BI on beta-carotene transport were additive, indicating that they may have different targets. Finally, differentiated Caco-2 cells treated with EZ showed a significant decrease in mRNA expression for the surface receptors SR-BI, Niemann-Pick type C1 Like 1 protein (NPC1L1), and ATP-binding cassette transporter, subfamily A (ABCA1) and for the nuclear receptors retinoid acid receptor (RAR)gamma, sterol-regulatory element binding proteins (SREBP)-1 and -2, and liver X receptor (LXR)beta as assessed by real-time PCR analysis. The data indicate that 1) EZ is an inhibitor of carotenoid transport, an effect that decreases with increasing polarity of the carotenoid molecule, 2) SR-BI is involved in carotenoid transport, and 3) EZ may act, not only by interacting physically with cholesterol transporters as previously suggested, but also by downregulating expression of these proteins. The cellular uptake and efflux of carotenoids, like that of cholesterol, likely involve more than one transporter.