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猪(野猪)有机阴离子转运多肽1a2的克隆与功能表征

Cloning and functional characterization of the pig (Sus scrofa) organic anion transporting polypeptide 1a2.

作者信息

Yu Yejin, Liu Xiaoxiao, Zhang Zheren, Xiao Yunpeng, Hong Mei

机构信息

College of Life Science, South China Agricultural University, Guangzhou, China.

出版信息

Xenobiotica. 2013 Aug;43(8):738-44. doi: 10.3109/00498254.2012.760762. Epub 2013 Jan 16.

DOI:10.3109/00498254.2012.760762
PMID:23323548
Abstract
  1. Organic anion transporting polypeptides (OATPs) are a family of transporter proteins that have been extensively recognized as key determinants of absorption, distribution, metabolism and excretion of various drugs. Human OATP1A2 has been demonstrated to transport wide spectrum of endogenous and exogenous compounds. Study on OATP1A2 orthologues of other species, however, is still limited. 2. Here, we described the cloning and functional characterization of a member of the OATP/Oatp family member obtained from pig (Sus scrofa) liver. Sequence analysis suggested that it has a high homology with human OATP1A2 and bovine Oatp1a2. Prototypic substrates estrone-3-sulfate (E-3-S) and taurocholic acid were transported by the protein. The transport of these two substrates is pH-dependent, with lower pH showing higher uptake function. Kinetic study showed the transport of these two substrates have a Km of 42.5 ± 12.1 and 33.1 ± 8.7 µM, respectively. Pig Slco1a2 has the highest expression level in the liver, and to a less extend in the brain and small intestine. 3. In conclusion, an OATP member was cloned from pig liver. Sequence analysis and phylogenic study revealed it as an orthologue of human OATP1A2. Its kinetic characteristic for prototypic substrates and organ distribution are similar with that of OATP1A2.
摘要
  1. 有机阴离子转运多肽(OATPs)是一类转运蛋白家族,已被广泛认为是各种药物吸收、分布、代谢和排泄的关键决定因素。人类OATP1A2已被证明可转运多种内源性和外源性化合物。然而,对其他物种OATP1A2直系同源物的研究仍然有限。2. 在此,我们描述了从猪肝中获得的OATP/Oatp家族成员之一的克隆及功能特性。序列分析表明,它与人类OATP1A2和牛Oatp1a2具有高度同源性。该蛋白可转运原型底物硫酸雌酮(E-3-S)和牛磺胆酸。这两种底物的转运依赖于pH值,较低的pH值显示出更高的摄取功能。动力学研究表明,这两种底物的转运Km值分别为42.5±12.1和33.1±8.7µM。猪Slco1a2在肝脏中的表达水平最高,在大脑和小肠中的表达水平较低。3. 总之,从猪肝中克隆了一个OATP成员。序列分析和系统发育研究表明它是人类OATP1A2的直系同源物。其对原型底物的动力学特征和器官分布与OATP1A2相似。

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