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肝细胞钠/胆汁酸共转运系统的功能表达克隆与特性研究

Functional expression cloning and characterization of the hepatocyte Na+/bile acid cotransport system.

作者信息

Hagenbuch B, Stieger B, Foguet M, Lübbert H, Meier P J

机构信息

Department of Medicine, University Hospital, Zürich, Switzerland.

出版信息

Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10629-33. doi: 10.1073/pnas.88.23.10629.

DOI:10.1073/pnas.88.23.10629
PMID:1961729
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC52983/
Abstract

Liver parenchymal cells continuously extract high amounts of bile acids from portal blood plasma. This uptake process is mediated by a Na+/bile acid cotransport system. A cDNA encoding the rat liver bile acid uptake system has been isolated by expression cloning in Xenopus laevis oocytes. The cloned transporter is strictly sodium-dependent and can be inhibited by various non-bile-acid organic compounds. Sequence analysis of the cDNA revealed an open reading frame of 1086 nucleotides coding for a protein of 362 amino acids (calculated molecular mass 39 kDa) with five possible N-linked glycosylation sites and seven putative transmembrane domains. Translation experiments in vitro and in oocytes indicate that the transporter is indeed glycosylated and that its polypeptide backbone has an apparent molecular mass of 33-35 kDa. Northern blot analysis with the cloned probe revealed crossreactivity with mRNA species from rat kidney and intestine as well as from liver tissues of mouse, guinea pig, rabbit, and man.

摘要

肝实质细胞持续从门静脉血浆中摄取大量胆汁酸。这种摄取过程由钠/胆汁酸共转运系统介导。通过在非洲爪蟾卵母细胞中进行表达克隆,已分离出编码大鼠肝脏胆汁酸摄取系统的cDNA。克隆的转运体严格依赖钠,并且可被多种非胆汁酸有机化合物抑制。对该cDNA的序列分析揭示了一个1086个核苷酸的开放阅读框,编码一个362个氨基酸的蛋白质(计算分子量为39 kDa),具有五个可能的N-连接糖基化位点和七个假定的跨膜结构域。体外和卵母细胞中的翻译实验表明,该转运体确实发生了糖基化,其多肽主链的表观分子量为33 - 35 kDa。用克隆探针进行的Northern印迹分析显示,该探针与大鼠肾脏、肠道以及小鼠、豚鼠、兔子和人类肝脏组织中的mRNA种类有交叉反应。

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Sodium-coupled taurocholate transport in the proximal convolution of the rat kidney in vivo and in vitro.大鼠肾脏近端曲部中钠偶联牛磺胆酸盐转运的体内及体外研究
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A simple method for displaying the hydropathic character of a protein.一种展示蛋白质亲水性特征的简单方法。
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Pharmacol Rev. 2024 Oct 16;76(6):1221-1253. doi: 10.1124/pharmrev.124.000978.
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The Food Contaminants Pyrrolizidine Alkaloids Disturb Bile Acid Homeostasis Structure-Dependently in the Human Hepatoma Cell Line HepaRG.食品污染物吡咯里西啶生物碱在人肝癌细胞系HepaRG中以结构依赖的方式扰乱胆汁酸稳态。
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