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IDENTIFICATION OF POTENT P-GLYCOPROTEIN (ABCB1) INHIBITORS IN CONTAMINATED SEDIMENT SAMPLES


Žaja, Roko; Senta, Ivan; Lončar, Jovica; Popović, Marta; Terzić, Senka; Ahel, Marijan; Smital, Tvrtko
IDENTIFICATION OF POTENT P-GLYCOPROTEIN (ABCB1) INHIBITORS IN CONTAMINATED SEDIMENT SAMPLES // Primo 16 - Pollutant Responses in Marine Organisms
Long Beach, CA, SAD, 2011. (poster, nije recenziran, neobjavljeni rad, znanstveni)


Naslov
IDENTIFICATION OF POTENT P-GLYCOPROTEIN (ABCB1) INHIBITORS IN CONTAMINATED SEDIMENT SAMPLES

Autori
Žaja, Roko ; Senta, Ivan ; Lončar, Jovica ; Popović, Marta ; Terzić, Senka ; Ahel, Marijan ; Smital, Tvrtko

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, neobjavljeni rad, znanstveni

Skup
Primo 16 - Pollutant Responses in Marine Organisms

Mjesto i datum
Long Beach, CA, SAD, 14.-18.05.2011

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
P-glycoprotein; EDA; sediment

Sažetak
P-glycoprotein (Pgp, abcb1) is a vital part of the multixenobiotic resistance (MXR) defense system in aquatic organisms and it is highly important to develop in vitro screening tools for identification of environmental contaminants that can interfere with its transport function. Recently, we selected and characterized doxorubicin resistant PLHC-1 cells sub-clone (PLHC-1/dox) which exhibits high over-expression of Pgp. Using PLHC-1/dox cells we also optimized fluorescent calcein-AM assay and the ATPase assay as reliable and specific in vitro methods for identification of compounds that can interact with fish Pgp. The main goal of our current study was to use developed in vitro tools paired with the so-called effect-directed analysis (EDA) approach to detect and identify Pgp interacting compounds in sediment samples collected at 6 differentially polluted sites at the Gorjak stream (Zagreb, Croatia), characterized by pronounced contamination from nearby pharmaceutical production facility. The sediment extracts showed high load of Pgp interacting compounds with the highest inhibitory potential associated with the site located immediately downstream from the facility. Initial fractionation of that sample revealed that Pgp inhibitory potential was almost exclusively associated with the major polar fraction, while medium and nonpolar fractions exhibited negligible effects on Pgp transport activity. We fractionated the polar fraction in 40 subfractions and found that 40% of inhibitory potential was specifically associated with fraction #30. As revealed by the ATPase assay, the prevailing types of interactions were non-competitive ones. Our chemical analysis revealed high abundance of polyethoxylate based surfactants and polypropylene glycols in the fraction #30. Finally, testing the series of standards with similar chemical structure we confirmed that this type of widely present contaminants may indeed act as potent Pgp inhibitors.

Izvorni jezik
Engleski

Znanstvena područja
Geologija, Biologija



POVEZANOST RADA


Projekt / tema
098-0982934-2712 - Organski spojevi kao molekulski obilježivači antropogenog utjecaja na okoliš (Marijan Ahel, )
098-0982934-2745 - Ekotoksikološko značenje ABC transportnih proteina u vodenih organizama (Tvrtko Smital, )

Ustanove
Institut "Ruđer Bošković", Zagreb