Analysis of functional significance of a newly discovered brain-specific transporter

我们专注于新发现的人脑特异性转运蛋白SLC10A4，它特异性地定位于黑质。利用人HepG2细胞成功构建了人SLC10A4的过表达细胞。在小肠中观察到SLC10A4介导的胆汁酸（如鹅去氧胆酸和熊去氧胆酸）摄取较低。使用免疫印迹分析在各种培养的细胞中研究SLC10A4的表达。最后，发现人脑来源的TE671（成神经管细胞瘤）细胞具有SLC 10A4的稳定表达。值得注意的是，在TE 671细胞中，凝血酶预处理诱导牛磺胆酸的摄取，并且Km值高于已知的牛磺胆酸钠共转运多肽，如ASBT和NTCP。我们认为，SLC10A4是一种特殊的脑转运蛋白，在血管损伤或组织损伤后发生凝血时，可被激活并负责胆汁酸的摄取。

We have focused on a newly discovered human brain-specific transporter SLC10A4, which is specifically localized in the substantia nigra. Over-expression cell of human SLC10A4 was successfully generated using human HepG2 cell. A low SLC10A4-mediated uptake of bile acids, such as chenodeoxycholic acid and ursodeoxycholic acid, was observed in the transformant. The expression of SLC10A4 was investigated in various cultured cells using immunoblot analysis. Finally, human brain-derived TE671(medulloblastoma) cells were found that they had a stable expression of SLC10A4. It was noteworthy finding that the uptake of taurocholic acid was induced by thrombin pretreatment in the TE671 cells and the Km value was higher than that of known sodium taurocholate co-transporting polypeptides, such as ASBT and NTCP. We considered that SLC10A4 was special brain transporter, could be activated and responsible for the uptake of bile acids when blood clotting was occurred following blood vessel damage or tissue injury.