CIIMAR/CIMAR - Interdisciplinary Centre of Marine and Environmental Research, Laboratory of Environmental Toxicology, University of Porto Porto, Portugal.
Front Physiol. 2014 Jul 22;5:266. doi: 10.3389/fphys.2014.00266. eCollection 2014.
ATP-binding cassette (ABC) proteins were first recognized for their role in multidrug resistance (MDR) in chemotherapeutic treatments, which is a major impediment for the successful treatment of many forms of malignant tumors in humans. These proteins, highly conserved throughout vertebrate species, were later related to cellular detoxification and accounted as responsible for protecting aquatic organisms from xenobiotic insults in the so-called multixenobiotic resistance mechanism (MXR). In recent years, research on these proteins in aquatic species has highlighted their importance in the detoxification mechanisms in fish thus it is necessary to continue these studies. Several transporters have been pointed out as relevant in the ecotoxicological context associated to the transport of xenobiotics, such as P-glycoproteins (Pgps), multidrug-resistance-associated proteins (MRPs 1-5) and breast cancer resistance associated protein (BCRP). In mammals, several nuclear receptors have been identified as mediators of phase I and II metabolizing enzymes and ABC transporters. In aquatic species, knowledge on co-regulation of the detoxification mechanism is scarce and needs to be addressed. The interaction of emergent contaminants that can act as chemosensitizers, with ABC transporters in aquatic organisms can compromise detoxification processes and have population effects and should be studied in more detail. This review intends to summarize the recent advances in research on MXR mechanisms in fish species, focusing in (1) regulation and functioning of ABC proteins; (2) cooperation with phase I and II biotransformation enzymes; and (3) ecotoxicological relevance and information on emergent pollutants with ability to modulate ABC transporters expression and activity. Several lines of evidence are clearly suggesting the important role of these transporters in detoxification mechanisms and must be further investigated in fish to underlay the mechanism to consider their use as biomarkers in environmental monitoring.
三磷酸腺苷结合盒（ABC）蛋白最初因其在化学治疗药物多药耐药（MDR）中的作用而被认识，这是人类许多恶性肿瘤成功治疗的主要障碍。这些在脊椎动物中高度保守的蛋白质后来与细胞解毒作用有关，并被认为是导致多药耐药机制（MXR）中保护水生生物免受异生物质侵害的原因。近年来，对水生物种中这些蛋白质的研究强调了它们在鱼类解毒机制中的重要性，因此有必要继续进行这些研究。已经指出几种转运蛋白在与异生物质转运相关的生态毒理学背景下具有相关性，例如 P 糖蛋白（Pgps）、多药耐药相关蛋白（MRPs 1-5）和乳腺癌耐药蛋白（BCRP）。在哺乳动物中，已经确定了几种核受体作为 I 相和 II 相代谢酶和 ABC 转运蛋白的调节剂。在水生物种中，关于解毒机制的共调节的知识很少，需要解决。新兴污染物作为化学增敏剂与水生生物中的 ABC 转运蛋白相互作用可能会破坏解毒过程并产生种群效应，应该更详细地研究。本综述旨在总结鱼类中 MXR 机制研究的最新进展，重点关注（1）ABC 蛋白的调节和功能；（2）与 I 相和 II 相生物转化酶的合作；（3）生态毒理学相关性和具有调节 ABC 转运蛋白表达和活性能力的新兴污染物信息。有几条证据清楚地表明这些转运蛋白在解毒机制中的重要作用，必须在鱼类中进一步研究，以阐明考虑将其用作环境监测生物标志物的机制。
