The role of MDR in the elimination of xenobiotics in farmed fish

在哺乳动物中，MDR等药物转运体在跨细胞外膜清除各种异源物质方面发挥着重要作用。然而，关于MDR在养殖鱼中的基因表达和功能的知识相对较少。在这里，我们研究了有机氯农药硫丹对尼罗罗非鱼肝脏多药耐药蛋白表达的影响。添加硫丹后，罗非鱼MDR的蛋白质水平呈时间依赖性增加。然而，多药耐药性水平与硫丹残留量之间的相关性较差。我们还从罗非鱼中分离了MDR及其调控因子PXR的全长cDNA。MDR和PXR基因均存在较多的多态性和物种差异。系统发育分析表明，与哺乳动物不同，鱼类MDR没有分化为MDR1和MDR3。虽然罗非鱼PXR和P-gp的mRNAs在不同的组织中都被检测到，但通过实时荧光定量聚合酶链式反应观察到了差异表达的模式。这些结果可能表明罗非鱼mdr1/3基因的转录调控机制与哺乳动物mdr1/3基因不同。

In mammals, drug transporters such as MDR play important roles for elimination of various xenobiotics across extra-cellular membranes. However, the knowledge about the gene expression and function of MDR in farmed fish are relatively modest. Here, we examined the expression of MDR protein in liver of Nile tilapia Oreochromis niloticus treated with the endosulfan, an organochloride pesticide. The protein level of tilapia MDR was increased in a time-dependent manner by feeding with endosulfan. However, there was poor correlation between MDR level and endosulfan residues. We also isolated the full-length cDNAs of MDR and its regulator, PXR from tilapia. A lot of polymorphisms and species difference were found in both MDR and PXR gene. Phylogenetic analysis indicated that, unlike mammal, fish MDR has not differentiated into MDR1 and MDR3. Although tilapia PXR and P-gp mRNAs were detected in various tissues, the differential expression patterns were observed by real-time PCR. These results may imply that the transcription of tilapia MDR is regulated by different mechanism from that of mammalian MDR1/3.