Roles of organic anion transporters in the renal excretion of perfluorooctanoic acid
Roles of organic anion transporters in the renal excretion of perfluorooctanoic acid
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DOI：
10.1111/j.1742-7843.2007.00155.x
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发表时间：
2008-07-01
影响因子：
3.1
通讯作者：
Koizumi, Akio
中科院分区：
文献类型：
--
作者：
Nakagawa, Hatsuki;Hirata, Taku;Koizumi, Akio
全氟辛酸是一种环境污染物，存在于野生动物和人类体内。全氟辛酸的肾脏排泄存在较大的种属和性别差异。在本研究中，我们的目的是表征有机阴离子转运蛋白1-3（OAT 1 -3）在人类和大鼠的全氟辛酸从肾脏的消除动力学的物种差异是否可以归因于这些转运蛋白的全氟辛酸的亲和力的差异。我们使用人（h）和大鼠（r）OAT瞬时表达细胞系统，并测量[（14）C]全氟辛酸转运活性。人和大鼠OAT 1和OAT 3介导的全氟辛酸转运程度相似。具体而言，h OAT 1的动力学参数K（m）分别为48.0 +/- 6.4 μ M; rOAT 1为51.0 +/- 12.0 μ M; hOAT 3为49.1 +/- 21.4 μ M; rOAT 3为80.2 +/- 17.8 μ M。这些数据表明，人和大鼠OAT 1和OAT 3对全氟辛酸具有高亲和力，其肾脏消除的种属差异并不归因于人和大鼠之间这些OAT的亲和力差异。相比之下，hOAT 2和rOAT 2均不转运全氟辛酸。总之，OAT 1和OAT 3介导的全氟辛酸转运在体外，这表明这些转运蛋白也运输全氟辛酸通过近端肾小管细胞的基底外侧膜在人体和大鼠体内。人和大鼠OAT 2均不介导全氟辛酸转运。总的来说，全氟辛酸在人类和大鼠体内半衰期的差异不太可能归因于这些转运体对全氟辛酸的亲和力差异。
Perfluorooctanoic acid, an environmental contaminant, is found in both wild animals and human beings. There are large species and sex differences in the renal excretion of perfluorooctanoic acid. In the present study, we aimed to characterize organic anion transporters 1-3 (OAT1-3) in human beings and rats to investigate whether the species differences in the elimination kinetics of perfluorooctanoic acid from the kidneys can be attributed to differences in the affinities of these transporters for perfluorooctanoic acid. We used human (h) and rat (r) OAT transient expression cell systems and measured the [(14)C] perfluorooctanoic acid transport activities. Both human and rat OAT1 and OAT3 mediated perfluorooctanoic acid transport to similar degrees. Specifically, the kinetic parameters, K(m), were 48.0 +/- 6.4 mu M for h OAT1; 51.0 +/- 12.0 mu M for rOAT1; 49.1 +/- 21.4 mu M for hOAT3 and 80.2 +/- 17.8 mu M for rOAT3, respectively. These data indicate that both human and rat OAT1 and OAT3 have high affinities for perfluorooctanoic acid and that the species differences in its renal elimination are not attributable to affinity differences in these OATs between human beings and rats. In contrast, neither hOAT2 nor rOAT2 transported perfluorooctanoic acid. In conclusion, OAT1 and OAT3 mediated perfluorooctanoic acid transport in vitro, suggesting that these transporters also transport perfluorooctanoic acid through the basolateral membrane of proximal tubular cells in vivo in both human beings and rats. Neither human nor rat OAT2 mediated perfluorooctanoic acid transport. Collectively, the difference between the perfluorooctanoic acid half-lives in human beings and rats is not likely to be attributable to differences in the affinities of these transporters for perfluorooctanoic acid.