Efflux of dietary flavonoid quercetin 4'-beta-glucoside across human intestinal Caco-2 cell monolayers by apical multidrug resistance-associated protein-2.
Efflux of dietary flavonoid quercetin 4'-beta-glucoside across human intestinal Caco-2 cell monolayers by apical multidrug resistance-associated protein-2.
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发表时间：
2000-09
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通讯作者：
R. Walgren;K. Karnaky;G. Lindenmayer;T. Walle
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作者：
R. Walgren;K. Karnaky;G. Lindenmayer;T. Walle
尽管有强有力的证据表明食用类黄酮有益于人类健康，但类黄酮被吸收的程度以及所涉及的机制仍存在争议。与常见的教条相反，我们之前证明槲皮素 4'-β-葡萄糖苷（最丰富的膳食类黄酮槲皮素的主要形式）不会被 Caco-2 单层细胞吸收。本研究的目的是检验特定外排转运蛋白导致吸收不足的假设。使用 Caco-2 单层细胞检查了槲皮素 4'-β-葡萄糖苷单独或与抑制剂一起的转运。此外，通过免疫荧光共聚焦显微镜检查了多药耐药相关蛋白 MRP1 和 MRP2 的亚细胞定位。槲皮素 4'-β-葡萄糖苷的流出是一个可饱和过程，不会被 P-糖蛋白抑制剂维拉帕米改变，但会被 MRP 抑制剂 MK-571 竞争性抑制。这些数据与 MRP2 顶膜的免疫荧光定位相结合，支持 MRP2 在槲皮素 4'-β-葡萄糖苷肠跨细胞流出中的作用。这些结果表明 MRP2 在运输一类新型物质（膳食葡萄糖苷）中发挥作用。
Although there is strong evidence to suggest that flavonoid consumption is beneficial to human health, the extent to which flavonoids are absorbed and the mechanisms involved are controversial. Contrary to common dogma, we previously demonstrated that quercetin 4'-beta-glucoside, the predominant form of the most abundant dietary flavonoid, quercetin, was not absorbed across Caco-2 cell monolayers. The aim of this study was to test the hypothesis that a specific efflux transporter is responsible for this lack of absorption. Transport of quercetin 4'-beta-glucoside, alone or with inhibitors, was examined with Caco-2 cell monolayers. In addition, subcellular localization of the multidrug resistance-associated proteins MRP1 and MRP2 was examined by immunofluorescent confocal microscopy. Efflux of quercetin 4'-beta-glucoside, a saturable process, was not altered by verapamil, a P-glycoprotein inhibitor, but was competitively inhibited by MK-571, an MRP inhibitor. These data in combination with immunofluorescent localization of MRP2 to the apical membrane support a role for MRP2 in the intestinal transcellular efflux of quercetin 4'-beta-glucoside. These results suggest a role for MRP2 in the transport of a new class of agents, dietary glucosides.