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

在哺乳动物中，药物转运蛋白如MDR在清除各种外源性物质的过程中发挥重要作用。然而，关于MDR基因在养殖鱼类中的表达和功能的知识相对有限。本文研究了有机氯农药硫丹对尼罗罗非鱼肝脏MDR蛋白表达的影响。罗非鱼MDR蛋白水平随时间的延长而升高。然而，MDR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及其调节因子PXR的全长cDNA。MDR基因和PXR基因均存在多态性和种属差异。系统发育分析表明，与哺乳动物不同，鱼类MDR没有分化为MDR 1和MDR 3。尽管罗非鱼PXR和P-gp mRNA在不同组织中均能检测到，但通过实时荧光定量PCR检测发现，二者的表达存在差异。这些结果可能暗示罗非鱼MDR的转录调控机制与哺乳动物MDR 1/3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.