Enhanced expression of basolateral multidrug resistance protein isoforms Mrp3 and Mrp5 in rat liver by LPS
Enhanced expression of basolateral multidrug resistance protein isoforms Mrp3 and Mrp5 in rat liver by LPS
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DOI：
10.1515/bc.2004.029
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发表时间：
2004-03-01
影响因子：
3.7
通讯作者：
Häussinger, D
中科院分区：
文献类型：
--
作者：
Donner, MG;Warskulat, U;Häussinger, D
脂多糖（LPS）诱导肝细胞下调和多药耐药蛋白2（Mrp2，Abcc2）的内吞修复。基底外侧Mrp亚型可补偿胆汁淤积中的细胞内代谢变化。因此，研究了LPS对大鼠肝脏中Mrp2和Mrp3的区域定位以及Mrp3、Mrp4、Mrp5和Mrp6 mRNA表达的影响。在正常大鼠肝脏中，在中心周围肝细胞中发现Mrp3也表达谷氨酰胺合成酶。在LPS处理的大鼠肝脏中，Mrp2蛋白的减少在中央周围肝细胞中最为明显，门静脉周围肝细胞中仅有轻微下调。相反，诱导Mrp3被发现在中心周围肝细胞与Mrp2的低表达。此外，我们发现Mrp5 mRNA的强烈诱导。同样，Mrp6 mRNA上调，但Mrp6蛋白表达没有显着改变。结论：Mrp3与Mrp2呈负相关，可能是对LPS诱导的静脉周围Mrp2缺失的一种补偿。中心周围Mrp3的诱导和Mrp5 mRNA的上调可能在LPS处理后肝细胞清除胆固醇物质和环核苷酸积累中起重要作用。
Lipopolysaccharide (LPS) induces hepatocellular downregulation and endocytic retrieval of multidrug resistance protein 2 (Mrp2, Abcc2). Basolateral Mrp isoforms may compensate for the intracellular metabolic changes in cholestasis. Therefore, the effect of LPS on the zonal localization of Mrp2 and Mrp3 and the expression of Mrp3, Mrp4, Mrp5, and Mrp6 mRNA were investigated in rat liver. In normal rat liver Mrp3 was found in pericentral hepatocytes also expressing glutamine synthetase. In LPStreated rat liver the decrease in Mrp2 protein was most pronounced in pericentral hepatocytes, with only minor downregulation in periportal hepatocytes. Conversely, induction of Mrp3 was found in pericentral hepatocytes with a low expression of Mrp2. Furthermore, we found a strong induction of Mrp5 mRNA. Likewise, Mrp6 mRNA was upregulated, however Mrp6 protein expression was not significantly altered. It is concluded that Mrp3 is inversely regulated to Mrp2 in a zonal pattern and may compensate for the LPSinduced loss of Mrp2 in the perivenous area. Induction of pericentral Mrp3 and upregulation of Mrp5 mRNA may play an important role in the hepatocellular clearance of cholephilic substances and cyclic nucleotides accumulating after LPS treatment.