Abstract
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.
Highlights
The maintenance of the overall environmental health is quite dependent on aquatic ecosystems
A few studies have been conducted in an attempt to elucidate this cooperative mechanism (Cooper et al, 1999; Sturm et al, 2001; Bard et al, 2002b; Paetzold et al, 2009; Costa et al, 2012b; Ferreira et al, 2014). The majority of these studies have been confined to the study of Permeability glycoprotein (Pgp) and CYP1A, and results suggest that these two proteins should not be coordinately regulated in fish, but enhance the fact that they may act in complementarity in cellular detoxification
The study of ATP-Binding Cassette (ABC) efflux transporters is very important from an environmental point of view, since they are believed to be an integral part of the cellular detoxification system
Summary
The maintenance of the overall environmental health is quite dependent on aquatic ecosystems. MULTIDRUG RESISTANCE (MDR) ASSOCIATED ABC TRANSPORTERS Juliano and Ling (1976) described a multidrug resistance (MDR) phenomenon, found in tumor cell lines of mammals, as the result of low intracellular accumulation of anti-cancer drugs, and related it with the overexpression of a transmembrane protein, responsible for an ATP-dependent efflux of those drugs into the extracellular medium This protein, denominated as Permeability glycoprotein (Pgp) and encoded by the ABCB1 gene, was the first ABC transporter to gain importance and later to be related to cellular detoxification. From this point, several other members of the ABC transporter efflux family, other than ABCB, have been identified as capable of interacting with endo- or xenobiotic compounds, including members of the ABCC and ABCG subfamilies (Cole and Deeley, 1998; Costa et al, 2012b; Fischer et al, 2013; Ferreira et al, 2014). The sister of P-glycoprotein (Spgp, ABCB11, BSEP), follows the same predicted structure as ABCB1 (Figure 2A), and studies
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
