Expression profiles of 50 xenobiotic transporter genes in humans and pre-clinical species: A resource for investigations into drug disposition
Expression profiles of 50 xenobiotic transporter genes in humans and pre-clinical species: A resource for investigations into drug disposition
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DOI：
10.1080/00498250600861751
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发表时间：
2006-10-01
期刊：
影响因子：
1.8
通讯作者：
Slatter, J. G.
中科院分区：
文献类型：
--
作者：
Bleasby, K.;Castle, J. C.;Slatter, J. G.
载体介导的转运蛋白在异生物质处置中起着关键作用，并且转运蛋白的研究由于物种差异及其选择性组织表达而变得复杂。本研究的目的是生成人类和临床前种属小鼠、大鼠、比格犬和食蟹猴中异生物质转运蛋白基因表达谱的综合数据集。采用基因芯片技术检测了40种人体组织中ABC、SLC和SLCO转运蛋白超家族50个基因的mRNA表达谱。转运蛋白基因，被确定为丰富的肝脏或肾脏，或选择其已知的作用，在异生物质处置，然后在22个组织在5个物种进行了比较。最后，由于药物反应和不良反应的临床变异性可能是转运蛋白基因表达变异性的结果，因此检查了75例人类肝脏供体中选定转运蛋白基因表达的变异性，并与高度变异的药物代谢酶CYP 3A4进行了比较。
Carrier-mediated transporters play a critical role in xenobiotic disposition and transporter research is complicated by species differences and their selective tissue expression. The purpose of this study was to generate a comprehensive data set of xenobiotic transporter gene expression profiles in humans and the pre-clinical species mouse, rat, beagle dog and cynomolgus monkey. mRNA expression profiles of 50 genes from the ABC, SLC and SLCO transporter superfamilies were examined in 40 human tissues by microarray analyses. Transporter genes that were identified as enriched in the liver or kidney, or that were selected for their known roles in xenobiotic disposition, were then compared in 22 tissues across the five species. Finally, as clinical variability in drug response and adverse reactions may be the result of variability in transporter gene expression, variability in the expression of selected transporter genes in 75 human liver donors were examined and compared with the highly variable drug metabolizing enzyme CYP3A4.