ATP-binding cassette multidrug transporters in Indian-rock oyster Saccostrea forskali and their role in the export of an environmental organic pollutant tributyltin

Kingtong, Sutin; Chitramvong, Yaowaluk; Janvilisri, Tavan

doi:10.1016/j.aquatox.2007.08.006

Cited by 49 publications

(29 citation statements)

References 52 publications

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“…In aquatic systems, much of our knowledge of the function of ABC transporters in marine invertebrates is limited to the response of these proteins under anthropogenic stress conditions (Kurelec 1992, Minier et al 1993, Smital et al 2000, Smital et al 2003, Kingtong et al 2007). However, for marine consumers that regularly feed on prey/hosts laden with natural toxins, efflux transporters may play a critical role in regulating the absorption of allelochemicals, thereby dictating diet selection.…”

Section: Discussionmentioning

confidence: 99%

Functional characterization and expression of molluscan detoxification enzymes and transporters involved in dietary allelochemical resistance

Whalen¹

2008

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Understanding how organisms deal with potentially toxic or fitness-reducing allelochemicals is important for understanding patterns of predation and herbivory in the marine environment. The ability of marine consumers to tolerate dietary toxins may involve biochemical resistance mechanisms, which increase the hydrophilicity of compounds and facilitate their active efflux out of sensitive cells and tissues. While several allelochemical-responsive detoxification enzymes have been sequenced and functionally characterized in terrestrial invertebrates feeding on chemically defended host plants, there is virtually no information concerning the role of these biotransformation enzymes that may mediate feeding tolerance in marine invertebrates. The objective of this research was to assess the diversity and dietary regulation of cytochrome P450s (CYP), glutathione S-transferases (GST) and ABC transporters in the generalist marine gastropod Cyphoma gibbosum feeding on a variety of chemically defended gorgonian corals, and to identify those dietary natural products that act as substrates for these proteins.Molecular and proteomic techniques identified both allelochemically-responsive CYPs, and constitutively expressed GSTs and transporters in Cyphoma digestive glands. Inhibition of Cyphoma GST activity by gorgonian extracts and selected allelochemicals (i.e., prostaglandins) indicated that gorgonian diets are likely to contain substrates for molluscan detoxification enzymes. In vitro metabolism studies with recombinant CYPs suggested those Cyphoma enzymes most closely related to vertebrate fatty acid hydroxylating enzymes may contribute to the detoxification ofichthyodeterrent cyclopentenone prostaglandins found in abundance in selected gorgonian species. Finally, the presence and activity of multixenobiotic resistance transporters in Cyphoma and the co-occuring specialist nudibranch, Tritonia hamnerorum, suggests these efflux transporters could function as a first line of defense against dietary intoxication. Together, these results suggest marine consumers that regularly exploit allelochemicalrich prey have evolved both general (GST and ABC transporters) and allelochemicalspecific (CYP) detoxification mechanisms to tolerate prey chemical defenses.Thesis Supervisor: Mark E. Hahn Title: Senior Scientist, Biology Department, WHOI COMPLETE ABSTRACT Intense consumer pressure in tropical marine ecosystems not only structures the organization and functioning of marine communities, but has a profound effect on the phenotype of resident organisms. In order to persist in the midst of extreme predation and herbivory, sessile benthic marine organisms, afforded with no means of escape, often produce chemical defenses, termed allelochemicals, which render their tissues unpalatable or toxic to most potential consumers. Despite the fitness-reducing consequences of consuming noxious/toxic prey, less mobile consumers, frequently drawn to their hosts by the chemical refugia they provide, are able to tolerate the toxicological challe...

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Section: Discussionmentioning

confidence: 99%

Functional characterization and expression of molluscan detoxification enzymes and transporters involved in dietary allelochemical resistance

Whalen¹

2008

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“…It is proposed that efflux pump mechanisms mediated by ABC transporters play a major role in elimination of multiple toxicants from the cell, a process called multi-xenobiotic resistance (MXR) [15]. In aquatic organisms, the presence of ABC transporters which are involved in MXR has been demonstrated [16]. In addition to extensively studied MDR1, several ABC transporters such as ABCC2 [17,18], ABCC3 [19] and BCRP [20] have been reported in fish.…”

Section: Introductionmentioning

confidence: 99%

Molecular analysis and heavy metal detoxification of ABCC1/MRP1 in zebrafish

Long

Cui

2010

Mol Biol Rep

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ABCC1/MRP1 belongs to the ATP-binding cassette superfamily and its elevated expression is closely associated with the multidrug resistance of various tumor cells. In normal tissues, ABCC1 confers resistance to a wide variety of xenobiotics and toxicants, demonstrating its important roles in tissue defense. Here, we report the cloning and functional characterization of abcc1 gene in zebrafish. This gene is localized on zebrafish chromosome 3 and contains a 4,557 bp open-reading frame. The deduced polypeptide is composed of 1,518 amino acids, which shares 70% identity with human ABCC1. Phylogenetic analysis revealed that ABCC1 proteins from thirteen vertebrate species are highly conserved during evolution. Transcriptional expression of zebrafish abcc1 gene in developing embryos was examined by whole-mount in situ hybridization and real-time PCR. Transcripts of zebrafish abcc1 gene were detectable in four-cell stage embryos, indicating that this gene is maternally expressed. ABCC1 mRNAs were ubiquitously distributed in embryos before 12 h post-fertilization (hpf) and mainly localized in eyes and brain from 24 to 72 hpf, and in gills from 96 to 120 hpf. In addition, zebrafish abcc1 gene was highly expressed in 1-hpf embryos and detected in all adult tissues examined, with highest expression in testis and lowest in heart and liver. Exposure of ZF4 cells and embryos to CdCl 2 Á2.5H 2 O, HgCl 2 , Pb(NO 3 ) 2 , or Na 3 AsO 4 Á12H 2 O significantly induced transcriptional expression of abcc1 gene. Furthermore, overexpression of abcc1 improved the survival rates of embryos exposed to Cd, Hg or As, while overexpression of a abcc1 mutant (ABCC1-G1420D) sensitized zebrafish embryos to toxic metals. These data indicate that zebrafish ABCC1 has crucial roles in heavy metals detoxification.

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“…The MRP proteins transport organic and inorganic anions, which are direct products of phase I and II metabolism present in the form of glutathione, glucuronic, or sulfate water soluble conjugates (Ballatori et al 2005;Cole and Deeley 2006). Studies have shown that MRP proteins are also capable to transport heavy metals including inorganic mercury (Aleo et al 2005;Kingtong et al 2007;Bošnjak et al 2009). …”

mentioning

confidence: 98%

“…For long it has been considered that the primary MXR transporter in aquatic organisms and their embryos is the P-gp. However, MRP proteins have also been recently recognized as major components of MXR defense in many aquatic organisms, both freshwater and marine, including mussels, sea urchins, and fish Sauerborn et al 2004;Kingtong et al 2007;Luckenbach and Epel 2008;Bošnjak et al 2009). The MRP proteins transport organic and inorganic anions, which are direct products of phase I and II metabolism present in the form of glutathione, glucuronic, or sulfate water soluble conjugates (Ballatori et al 2005;Cole and Deeley 2006).…”

mentioning

confidence: 99%

Sea Urchin Embryotoxicity Test for Environmental Contaminants—Potential Role of the MRP Proteins

Bošnjak

Šegvić

Smital

et al. 2010

Water Air Soil Pollut

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The main goals of this study were (1) to standardize a simple and reliable embryotoxicity test for environmental contaminants and (2) to evaluate the presence and possible protective role of the multidrug resistance-associated (MRP) protein-mediated multixenobiotic defense in two Mediterranean sea urchin species, Paracentrotus lividus and Arbacia lixula. Toxic end-point used was the success of the first cell division in sea urchin embryos. Embryotoxicities of three environmentally relevant contaminants: mercuric chloride (HgCl 2 , 0.05-6 μM), trybutiltin (TBT, 2.5-500 nM), and oxybenzone (OXI, 0.1-100 μM); as well as seawater samples collected from the polluted and unpolluted locations, were determined and compared. A. lixula embryos were more sensitive to all three toxic compounds, and both P. lividus and A. lixula embryos were highly sensitive to TBT at nanomolar concentrations (EC 50 49±5 and 36.8±3 nM, respectively). Inhibition of MRP protein by specific inhibitor MK571 caused significant increase in embryotoxic potency of HgCl 2 (EC 50 0.697±0.03 and 0.245±0.04 μM, respectively), TBT (EC 50 24±3 and 7.4±1 nM, respectively) and polluted seawater sample, but not of OXI or unpolluted, natural seawater. Therefore, our results demonstrated for the first time the protective relevance of MRP proteins in early development of these two Mediterranean sea urchin species. Finally, the embryotoxicity protocol described in this study represents a simple and rapid bioassay for determination of environmentally relevant seawater contamination.

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ATP-binding cassette multidrug transporters in Indian-rock oyster Saccostrea forskali and their role in the export of an environmental organic pollutant tributyltin

Cited by 49 publications

References 52 publications

Functional characterization and expression of molluscan detoxification enzymes and transporters involved in dietary allelochemical resistance

Functional characterization and expression of molluscan detoxification enzymes and transporters involved in dietary allelochemical resistance

Molecular analysis and heavy metal detoxification of ABCC1/MRP1 in zebrafish

Sea Urchin Embryotoxicity Test for Environmental Contaminants—Potential Role of the MRP Proteins

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