ABC transporters in fish species: a review

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.

Combination effects of nano-TiO2 and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on biotransformation gene expression in the liver of European sea bass Dicentrarchus labrax

“…A less sensitivity of Abcb1 upon exposure to 2,3,7,8-TCDD as well as nano-TiO 2 has been observed in our study for single chemicals exposure while fish exposed to both showed a significant down regulation of Abcb1 gene expression. Our findings are in agreement with previous work done on fish species in which Abcb1 gene results less responsive and even more difficult to assess as reported for instance in sea bass by Ferreira et al (2014) while Abcc1-2 and Abcg2 are generally up-regulated by different xenobiotics.…”

“…The similarities observed for Abcb1, Abcc1-1 and Abcg2 genes with other fish and mammals confirm the suitability of liver gene expression profile for ecotoxicological studies in order to increase the current knowledge on their role in organ defense from toxicant exposure (Ferreira et al, 2014;Luckenbach et al, 2014). According to the literature, contradictory results are present on ABC gene expression in liver of fish species upon exposure to aquatic toxicants including polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) including dioxin-like PCBs.…”

Adaptive capabilities and fitness consequences associated with pollution exposure in fish

“…Physiological acclimatization of fish to metals involves increased proliferation and hypertrophy of mucus-producing goblet cells; mucus chelates metals, reducing their availability [48]. MDR1, which pumps xenobiotics (such as toxins or drugs) back into the intestinal lumen, is a prime candidate for transport-related adaptation in fish [49]. The expression of this gene in F. heteroclitus from a contaminated site was shown to be two- to threefold higher than in fish from reference sites, but whether this resulted from adaptation is not known [50].…”

An engineered Abcb4 expressing model reveals the central role of NF-κB in the regulation of drug resistance in zebrafish

“…protein plays a similar role to P-gp protein [23]. Importantly, the expression pattern of Abcb4 in zebrafish which is similar to ABCB1 gene, mainly distributed in brain and intestinal tissues [24].…”