Organic anion transporting polypeptides and organic cation transporter 1 contribute to the cellular uptake of the flavonoid quercetin
Organic anion transporting polypeptides and organic cation transporter 1 contribute to the cellular uptake of the flavonoid quercetin
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DOI：
10.1007/s00210-014-1000-6
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发表时间：
2014-09-01
影响因子：
3.6
通讯作者：
Mandery, Kathrin
中科院分区：
文献类型：
--
作者：
Glaeser, Hartmut;Bujok, Krystyna;Mandery, Kathrin
黄酮类化合物如槲皮素和山奈酚介导几种健康保护作用，例如，抗癌作用。它们是有机阴离子转运多肽（OATP）和有机阳离子转运蛋白（例如，OCT 2）。然而，很少有人知道是否这样的转运蛋白有助于细胞摄取类黄酮。因此，我们使用稳定表达不同人OATP或OCT 1的HEK 293细胞系研究了山奈酚和槲皮素的细胞摄取。山奈酚不是任何研究的转运蛋白（OATP 1A 2、OATP 1B 1、OATP 1B 3、OATP 2A 1、OATP 2B 1、OATP 3A 1、OATP 4A 1、OATP 5A 1和OCT 1）的底物。与对照细胞相比，槲皮素在HEK 293-OATP 1A 2、HEK 293-OATP 2A 1、HEK 293-OATP 2B 1和HEK 293-OCT 1细胞中的摄取显著更高。OATP 1A 2-、OATP 2B 1-和OCT 1-介导的槲皮素摄取分别受到已知抑制剂（如柚苷、环孢菌素A和奎尼丁）的抑制。前列腺素E-2和双氯芬酸未抑制槲皮素在HEK 293-OATP 2A 1细胞中的细胞蓄积。离子载体羰基氰化物4-（三氟甲氧基）苯腙（FCCP）通过增加HEK 293对照细胞中的摄取减少了槲皮素的净摄取，但在HEK 293-OATP 2B 1细胞中未引起显著变化，表明槲皮素遵循FCCP驱动的质子通量通过质膜。除了被动扩散外，SLC转运蛋白OATP 1A 2、OATP 2B 1和OCT 1也有助于槲皮素的细胞蓄积。
Flavonoids such as quercetin and kaempferol mediate several health protective effects, e.g., anticancer effects. They are inhibitors of organic anion transporting polypeptides (OATP) and organic cation transporters (e.g., OCT2). However, little is known whether such transporters contribute to the cellular uptake of flavonoids. Therefore, we investigated the cellular uptake of kaempferol and quercetin using HEK293 cell lines stably expressing different human OATPs or OCT1. Kaempferol was not a substrate of any of the investigated transporters (OATP1A2, OATP1B1, OATP1B3, OATP2A1, OATP2B1, OATP3A1, OATP4A1, OATP5A1, and OCT1). Quercetin showed a significantly higher uptake into the HEK293-OATP1A2, HEK293-OATP2A1, HEK293-OATP2B1, and HEK293-OCT1 cells compared to control cells. The OATP1A2-, OATP2B1-, and OCT1-mediated quercetin uptake was inhibited by known inhibitors such as naringin, cyclosporin A, and quinidine, respectively. The cellular accumulation of quercetin into HEK293-OATP2A1 cells was not inhibited by prostaglandin E-2 and diclofenac. The ionophore carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) reduced the net uptake of quercetin by increasing the uptake in the HEK293-control cells and causing no significant change in the HEK293-OATP2B1 cells indicating that quercetin follows the FCCP-driven proton flux through the plasma membrane. In addition to passive diffusion, the SLC transporters OATP1A2, OATP2B1, and OCT1 contribute to cellular accumulation of quercetin.