Chemical effects on dye efflux activity in live zebrafish embryos and on zebrafish Abcb4 ATPase activity

被引:19
作者
Bieczynski, Flavia [1 ,2 ]
Burkhardt-Medicke, Kathleen [2 ]
Luquet, Carlos M. [3 ]
Scholz, Stefan [2 ]
Luckenbach, Till [2 ]
机构
[1] Univ Nacl Comahue UNCo, Ctr Invest Toxicol Ambiental & Agrobiotecnol Coma, Consejo Nacl Invest Cient & Tecn CONICET, Fac Ingn, Buenos Aires, Neuquen, Argentina
[2] UFZ Helmholtz Ctr Environm Res, Dept Bioanalyt Ecotoxicol, Permoserstr 15, D-04318 Leipzig, Germany
[3] Subsede INIBIOMA CEAN CONICET UNCo, Lab Ecotoxicol Acuat, Junin De Los Andes, Neuquen, Argentina
关键词
ABC efflux transporter; ATPase activity; chemosensitizer; dye accumulation assay; zebrafish Abcb4; zebrafish embryo; MULTIXENOBIOTIC RESISTANCE MECHANISM; PERSONAL CARE PRODUCTS; P-GLYCOPROTEIN ASSAYS; MULTIDRUG-RESISTANCE; TRANSPORTER ACTIVITY; DANIO-RERIO; GENE; DRUGS; PHARMACEUTICALS; RECONSTITUTION;
D O I
10.1002/1873-3468.14015
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
ATP-binding cassette (ABC) transporter proteins include efflux pumps that confer multixenobiotic resistance to zebrafish embryos, a valuable toxico/pharmacological model. Here, we established an automated microscopy-based rhodamine B dye accumulation assay in which enhanced dye accumulation in live zebrafish embryos indicates inhibition of multixenobiotic efflux transporter activity. Twenty structurally divergent known substrates and/or inhibitors of human ABC transporters and environmentally relevant compounds were examined using this assay and the ATPase activity of recombinant zebrafish Abcb4 as readouts. These two assays confirmed that Abcb4 functions as an efflux transporter in zebrafish, whereas they gave discordant results for some of the tested substances. The dye accumulation assay in zebrafish embryos could be useful to screen environmental pollutants and other chemicals for efflux transporter interaction in a medium-throughput fashion.
引用
收藏
页码:828 / 843
页数:16
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