Localization of the sulfate/anion exchanger in the rat liver

Localization of the sulfate/anion exchanger in the rat liver
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DOI:
10.1152/ajpgi.00492.2005
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发表时间:
2006-05-01
影响因子:
4.5
通讯作者:
Burckhardt, BC
Burckhardt, BC
中科院分区:
医学2区
文献类型:
--
作者:
Quondamatteo, F;Krick, W;Burckhardt, BC

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虽然硫酸盐/阴离子转运蛋白(sat-1; SLC26A1)通过表达克隆从大鼠肝脏cDNA文库中分离出来,但sat-1在肝脏中的定位及其在硫酸盐和有机硫酸盐运输中的作用仍未得到解决。原位杂交和免疫组织化学研究证实了肝组织中sat-1的定位。对分离的肝细胞和培养的肝内皮细胞和星状细胞进行RT-PCR研究,以检测这些细胞中是否存在sat-1。在硫酸盐吸收和外排实验中,评估了sat-1的底物特异性。肝细胞和内皮细胞中均有Sat-1 mRNA表达。Sat-1蛋白定位于肝窦膜和肝细胞边界。小管区及胆毛细血管未见染色。磺胺酰利尿剂或有机硫酸盐对硫酸盐摄取的影响较小。在碳酸氢盐的存在下,表达sat-1的卵母细胞的硫酸盐外排增强,表明硫酸盐/碳酸氢盐交换。硫酸雌酮不经sat-1转运。Sat-1可能负责将血液中的无机硫酸盐吸收到肝细胞中,从而使硫酸化反应成为可能。在肝细胞和内皮细胞中,sat-1也可能为蛋白聚糖的合成提供硫酸盐。
Although the sulfate/anion transporter (sat-1; SLC26A1) was isolated from a rat liver cDNA library by expression cloning, localization of sat-1 within the liver and its contribution to the transport of sulfate and organo sulfates have remained unresolved. In situ hybridization and immunohistochemical studies were undertaken to demonstrate the localization of sat-1 in liver tissue. RT-PCR studies on isolated hepatocytes and liver endothelial and stellate cells in culture were performed to test for the presence of sat-1 in these cells. In sulfate uptake and efflux experiments, the substrate specificity of sat-1 was evaluated. Sat-1 mRNA was found in hepatocytes and endothelial cells. Sat-1 protein was localized in sinusoidal membranes and along the borders of hepatocytes. The canalicular region and bile capillaries were not stained. Sulfate uptake was only slightly affected by sulfamoyl diuretics or organo sulfates. Sulfate efflux from sat-1-expressing oocytes was enhanced in the presence of bicarbonate, indicating sulfate/bicarbonate exchange. Estrone sulfate was not transported by sat-1. Sat-1 may be responsible for the uptake of inorganic sulfate from the blood into hepatocytes to enable sulfation reactions. In hepatocytes and endothelial cells, sat-1 may also supply sulfate for proteoglycan synthesis.