Zaja Roko, Munić Vesna, Smital Tvrtko
Laboratory for Molecular Ecotoxicology, Division for Marine and Environmental Research, Ruder Bosković Institute, Bijenicka 54, Zagreb, Croatia.
Mar Environ Res. 2008 Jul;66(1):77-9. doi: 10.1016/j.marenvres.2008.02.028. Epub 2008 Feb 26.
As has been recently demonstrated in mammals, apart from the P-glycoprotein (Pgp, ABCB) and the MRP-like proteins (MRPs, ABCC), another efflux transporter - the BCRP (ABCG2) - expressed in polarized epithelial cells of different tissues, is involved in regulation of intestinal absorption and biliary excretion of potentially toxic xenobiotics. However, no study has been directed towards identification of BCRP (ABCG2) in fish species. In the present study we have cloned the full ABCG2 transcript from rainbow trout (Oncorhynchus mykiss) liver, showing a high sequence identity (60%) to human ABCG2 gene. Using Real-Time PCR we measured relative expression of ABCG2 in trout liver and primary hepatocytes and compared these expression levels to the expression of other ABC transporters expressed in apical membrane of hepatocytes (ABCB1, ABCB11 and ABCC2). ABCG2 expression was 6-fold higher than ABCC2 and almost 42 fold higher than ABCB1, indicating that the ABCG2 probably plays a significant role in the overall disposition and excretion of xenobiotics in fish.
最近在哺乳动物中已经证实,除了P-糖蛋白(Pgp,ABCB)和多药耐药相关蛋白(MRPs,ABCC)之外,另一种外排转运蛋白——乳腺癌耐药蛋白(BCRP,ABCG2),在不同组织的极化上皮细胞中表达,参与调节潜在毒性外源性物质的肠道吸收和胆汁排泄。然而,尚未有针对鱼类中BCRP(ABCG2)的鉴定研究。在本研究中,我们从虹鳟(Oncorhynchus mykiss)肝脏中克隆了完整的ABCG2转录本,其与人类ABCG2基因具有较高的序列同一性(60%)。使用实时定量PCR,我们测量了虹鳟肝脏和原代肝细胞中ABCG2的相对表达,并将这些表达水平与肝细胞顶端膜中表达的其他ABC转运蛋白(ABCB1、ABCB11和ABCC2)的表达进行比较。ABCG2的表达比ABCC2高6倍,比ABCB1高近42倍,这表明ABCG2可能在鱼类对外源性物质的整体处置和排泄中发挥重要作用。