Centre for Drug Research, University of Helsinki, Helsinki, Finland.
J Pharm Sci. 2010 Feb;99(2):1087-98. doi: 10.1002/jps.21878.
ATP-binding cassette (ABC) transporters are able to efflux their substrate drugs from the cells. We compared expression of efflux proteins in normal human corneal epithelial tissue, primary human corneal epithelial cells (HCEpiC), and corneal epithelial cell culture model (HCE model) based on human immortal cell line. Expression of multidrug resistance protein 1 (MDR1), multidrug resistance-associated protein 1-6 (MRP1-6) and breast cancer resistance protein (BCRP) was studied using quantitative RT-PCR, Western blot, and immunohistochemistry. Only MRP1, MRP5, and BCRP were expressed in the freshly excised human corneal epithelial tissue. Expression of MRP1 and MRP5 was localized predominantly in the basal cells of the central cornea and limbus. Functional efflux activity was shown in the cell models, but they showed over-expression of most efflux transporters compared to that of normal corneal epithelium. In conclusion, MRP1, MRP5, and BCRP are expressed in the corneal epithelium, but MDR1, MRP2, MRP3, MRP4, and MRP6 are not significantly expressed. HCE cell model and commercially available primary cells deviate from this expression profile.
三磷酸腺苷结合盒（ABC）转运蛋白能够将其底物药物从细胞内排出。我们比较了正常人类角膜上皮组织、原代人角膜上皮细胞（HCEpiC）和基于人永生化细胞系的角膜上皮细胞培养模型（HCE 模型）中流出蛋白的表达。使用定量 RT-PCR、Western blot 和免疫组织化学研究了多药耐药蛋白 1（MDR1）、多药耐药相关蛋白 1-6（MRP1-6）和乳腺癌耐药蛋白（BCRP）的表达。在新鲜切取的人角膜上皮组织中仅表达 MRP1、MRP5 和 BCRP。MRP1 和 MRP5 的表达主要定位于中央角膜和角膜缘的基底细胞中。在细胞模型中显示出了功能流出活性，但与正常角膜上皮相比，它们表现出大多数流出转运蛋白的过度表达。总之，MRP1、MRP5 和 BCRP 在角膜上皮中表达，但 MDR1、MRP2、MRP3、MRP4 和 MRP6 表达不明显。HCE 细胞模型和市售的原代细胞偏离了这种表达模式。
