Click
here to close Hello! We notice that
you are using Internet Explorer, which is not supported by Echinobase
and may cause the site to display incorrectly. We suggest using a
current version of Chrome,
FireFox,
or Safari.
Ecotoxicology
2011 Mar 01;202:419-28. doi: 10.1007/s10646-011-0593-5.
Show Gene links
Show Anatomy links
Influence of P-glycoprotein on embryotoxicity of the antifouling biocides to sea urchin (Strongylocentrotus intermedius).
Xu X
,
Fu J
,
Wang H
,
Zhang B
,
Wang X
,
Wang Y
.
???displayArticle.abstract??? P-glycoprotein (P-gp), as an ATP-binding cassette transporter, transports a wide variety of substrates varying from small molecules like steroids to large polypeptides across the cell membrane in human and animals, even in aquatic animals. Although P-gp protein has attracted much attention of research, its effect on the toxicity of environmental toxicants such as antifouling biocides is still poorly understood. The goal of this study is to evaluate whether copper pyrithione (CuPT), Sea-Nine 211, dichlofluanid and tolylfluanid, four widely used antifouling agents, can be transported by P-gp in embryos of sea urchin Strongylocentrotus intermedius in the presence and absence of the P-gp inhibitor verapamil. Cytotoxcicities of Sea-Nine 211 (EC50 = 99 nM, at 4-arm pluteus) and dichlofluanid (EC50 = 144 nM, at multi-cell) are enhanced by the addition of the P-gp inhibitor, indicating that the two biocides are potential P-gp substrates. Tolylfluanid and CuPT are not transported by P-gp out of the cell, since no obvious changes in the cytotoxicities of the two biocides are observed no matter whether verapamil is added or not. In addition, to understand the mechanisms of ligand binding and its interaction with P-gp, a three-dimensional model of the sea urchin P-gp is generated based on the mouse crystal structure by using homology modeling approach. With this model, a flexible docking is performed and the results indicate that Sea-Nine 211 and dichlofluanid share the same binding site with verapamil, composed of key residues Lys677, Lys753, Thr756, Ala780, Met1033 and Phe1037, whereas tolylfluanid and CuPT display totally different binding modes to P-gp. This further demonstrates that Sea-Nine 211 and dichlofluanid are P-gp substrates, which provides us with new insights into the interactions of P-gp with the antifouling contaminants in aquatic invertebrate embryos.
Aller,
Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding.
2009, Pubmed
Aller,
Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding.
2009,
Pubmed
Alzieu,
Environmental impact of TBT: the French experience.
2000,
Pubmed
Balayssac,
Does inhibition of P-glycoprotein lead to drug-drug interactions?
2005,
Pubmed
Bellas,
Toxicity of the booster biocide Sea-Nine to the early developmental stages of the sea urchin Paracentrotus lividus.
2007,
Pubmed
,
Echinobase
Boiocchi,
Mechanism of multidrug resistance in human tumour cell lines and complete reversion of cellular resistance.
1992,
Pubmed
Epel,
The sea urchin embryo as a model for studying efflux transporters: roles and energy cost.
2006,
Pubmed
,
Echinobase
Ford,
Pharmacology of drugs that alter multidrug resistance in cancer.
1990,
Pubmed
Gatidou,
Fate of Irgarol 1051, diuron and their main metabolites in two UK marine systems after restrictions in antifouling paints.
2007,
Pubmed
Hamdoun,
Activation of multidrug efflux transporter activity at fertilization in sea urchin embryos (Strongylocentrotus purpuratus).
2004,
Pubmed
,
Echinobase
Harino,
Concentrations of antifouling biocides in sediment and mussel samples collected from Otsuchi bay, Japan.
2007,
Pubmed
Higgins,
Multiple molecular mechanisms for multidrug resistance transporters.
2007,
Pubmed
Jain,
Surflex: fully automatic flexible molecular docking using a molecular similarity-based search engine.
2003,
Pubmed
Koutsaftis,
Toxicity of four antifouling biocides and their mixtures on the brine shrimp Artemia salina.
2007,
Pubmed
Kueh,
Monitoring of toxic substances in the Hong Kong marine environment.
2008,
Pubmed
Leslie,
Multidrug resistance proteins: role of P-glycoprotein, MRP1, MRP2, and BCRP (ABCG2) in tissue defense.
2005,
Pubmed
Loo,
Defining the drug-binding site in the human multidrug resistance P-glycoprotein using a methanethiosulfonate analog of verapamil, MTS-verapamil.
2001,
Pubmed
Porretta,
Defence mechanisms against insecticides temephos and diflubenzuron in the mosquito Aedes caspius: the P-glycoprotein efflux pumps.
2008,
Pubmed
Shabbir,
Differential effects of the organochlorine pesticide DDT and its metabolite p,p'-DDE on p-glycoprotein activity and expression.
2005,
Pubmed
Thomas,
Increased persistence of antifouling paint biocides when associated with paint particles.
2003,
Pubmed
Thompson,
CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice.
1994,
Pubmed
Townsin,
The ship hull fouling penalty.
2003,
Pubmed
Varma,
P-glycoprotein inhibitors and their screening: a perspective from bioavailability enhancement.
2003,
Pubmed
Venn,
P-glycoprotein (multi-xenobiotic resistance) and heat shock protein gene expression in the reef coral Montastraea franksi in response to environmental toxicants.
2009,
Pubmed
Voulvoulis,
Comparative environmental assessment of biocides used in antifouling paints.
2002,
Pubmed
Wang,
Classification of substrates and inhibitors of P-glycoprotein using unsupervised machine learning approach.
2005,
Pubmed
Whalen,
The role of multixenobiotic transporters in predatory marine molluscs as counter-defense mechanisms against dietary allelochemicals.
2010,
Pubmed
Xu,
Acute toxicity and synergism of binary mixtures of antifouling biocides with heavy metals to embryos of sea urchin Glyptocidaris crenularis.
2011,
Pubmed
,
Echinobase
Xu,
Assessment of toxic interactions of heavy metals in multi-component mixtures using sea urchin embryo-larval bioassay.
2011,
Pubmed
,
Echinobase
Yusa,
Reversal mechanism of multidrug resistance by verapamil: direct binding of verapamil to P-glycoprotein on specific sites and transport of verapamil outward across the plasma membrane of K562/ADM cells.
1989,
Pubmed
van Tellingen,
The importance of drug-transporting P-glycoproteins in toxicology.
2001,
Pubmed