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Pregled bibliografske jedinice broj: 545314

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Autori: Žaja, Roko; Senta, Ivan; Lončar, Jovica; Popović, Marta; Terzić, Senka; Ahel, Marijan; Smital, Tvrtko
Naslov: IDENTIFICATION OF POTENT P-GLYCOPROTEIN (ABCB1) INHIBITORS IN CONTAMINATED SEDIMENT SAMPLES
( IDENTIFICATION OF POTENT P-GLYCOPROTEIN (ABCB1) INHIBITORS IN CONTAMINATED SEDIMENT SAMPLES )
Izvornik:
Skup: Primo 16 - Pollutant Responses in Marine Organisms
Mjesto i datum: Long Beach, CA, SAD, 14.-18.05.2011.
Ključne riječi: P-glycoprotein; EDA; sediment
( 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.
Vrsta sudjelovanja: Poster
Vrsta prezentacije u zborniku: Nije objavljen
Vrsta recenzije: Nema recenziju
Projekt / tema: 098-0982934-2745, 098-0982934-2712
Izvorni jezik: eng
Kategorija: Znanstveni
Znanstvena područja:
Geologija,Biologija
Upisao u CROSBI: smital@irb.hr (smital@irb.hr), 18. Stu. 2011. u 17:15 sati



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