Luckenbach Till, Fischer Stephan, Sturm Armin
Department of Bioanalytical Ecotoxicology, UFZ-Helmholtz Centre for Environmental Research, 04318 Leipzig, Germany.
Department of Environmental Toxicology, Eawag, Swiss Federal Institute of Aquatic Science and Technology, 8600 Dübendorf, Switzerland; Department of Environmental Systems Sciences, ETH Zürich, Institute of Biogeochemistry and Pollutant Dynamics, 8092 Zürich, Switzerland.
Comp Biochem Physiol C Toxicol Pharmacol. 2014 Sep;165:28-52. doi: 10.1016/j.cbpc.2014.05.002. Epub 2014 May 22.
Most members of the large ATP-binding cassette (ABC) gene family are transporters involved in substrate translocation across biological membranes. In eukaryotes, ABC proteins functioning as drug transporters are located in the plasma membrane and mediate the cellular efflux of a wide range of organic chemicals, with some transporters also transporting certain metals. As the enhanced expression of ABC drug transporters can confer multidrug resistance (MDR) to cancers and multixenobiotic resistance (MXR) to organisms from polluted habitats, these ABC family members are also referred to as MDR or MXR proteins. In mammals, ABC drug transporters show predominant expression in tissues involved in excretion or constituting internal or external body boundaries, where they facilitate the excretion of chemicals and their metabolites, and limit chemical uptake and penetration into "sanctuary" sites of the body. Available knowledge about ABC proteins is still limited in teleost fish, a large vertebrate group of high ecological and economic importance. Using transport activity measurements and immunochemical approaches, early studies demonstrated similarities in the tissue distribution of ABC drug transporters between teleosts and mammals, suggesting conserved roles of the transporters in the biochemical defence against toxicants. Recently, the availability of teleost genome assemblies has stimulated studies of the ABC family in this taxon. This review summarises the current knowledge regarding the genetics, functional properties, physiological function, and ecotoxicological relevance of teleostean ABC transporters. The available literature is reviewed with emphasis on recent studies addressing the tissue distribution, substrate spectrum, regulation, physiological function and phylogenetic origin of teleostean ABC transporters.
大型ATP结合盒（ABC）基因家族的大多数成员都是参与底物跨生物膜转运的转运蛋白。在真核生物中，作为药物转运蛋白发挥作用的ABC蛋白位于质膜中，介导多种有机化学物质的细胞外排，一些转运蛋白还能转运某些金属。由于ABC药物转运蛋白的表达增强可使癌症产生多药耐药性（MDR），并使来自污染栖息地的生物体产生多异生物耐药性（MXR），这些ABC家族成员也被称为MDR或MXR蛋白。在哺乳动物中，ABC药物转运蛋白在参与排泄或构成身体内部或外部边界的组织中表达占主导地位，在这些组织中它们促进化学物质及其代谢产物的排泄，并限制化学物质的摄取和渗透到身体的“庇护所”部位。在硬骨鱼（一种具有高度生态和经济重要性的大型脊椎动物类群）中，关于ABC蛋白的现有知识仍然有限。早期研究通过转运活性测量和免疫化学方法，证明了硬骨鱼和哺乳动物之间ABC药物转运蛋白在组织分布上的相似性，表明这些转运蛋白在针对毒物的生化防御中具有保守作用。最近，硬骨鱼基因组组装的可得性激发了对该分类群中ABC家族的研究。这篇综述总结了关于硬骨鱼ABC转运蛋白的遗传学、功能特性、生理功能和生态毒理学相关性的当前知识。本文回顾了现有文献，重点关注近期关于硬骨鱼ABC转运蛋白的组织分布、底物谱、调控、生理功能和系统发育起源的研究。
