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

我们重点研究了一种新发现的人脑特异转运蛋白SLC10A4，它特异地定位于黑质。利用人HepG2细胞成功构建了人SLC10A4高表达细胞。在转化子中观察到SLC10A4对鹅去氧胆酸和熊去氧胆酸等胆汁酸的低摄取。用免疫印迹法检测SLC10A4在不同培养细胞中的表达。最后，人脑来源的TE671(髓母细胞瘤)细胞被发现有稳定的SLC10A4表达。值得注意的是，凝血酶可诱导TE671细胞摄取牛磺胆酸，其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，当血管损伤或组织损伤后发生凝血时，SLC10A4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.