Coordinate induction by antioxidants of UDP-glucuronosyltransferase UGT1A6 and the apical conjugate export pump MRP2 (multidrug resistance protein 2) in Caco-2 cells.
Treatment of Caco-2 cells with the antioxidants quercetin or t-butylhydroquinone led to induced protein levels of UDP-glucuronosyltransferase UGT1A6 (ca. 3-fold over controls) and of the apical conjugate export pump multidrug resistance protein 2 (MRP2; 1.9-fold over controls). In contrast to UGT1A6, MRP2 (symbol ABCC2) was not inducible by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Immunocytochemistry demonstrated that MRP2 was only expressed at the brush border domain of Caco-2 cell monolayers. The results indicate that UGT1A6 and MRP2 are coordinately induced by antioxidants, facilitating chemoprotection against phenolic toxins and excretion of conjugates into the intestinal lumen.
Bock
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KW
Institute of Toxicology, University of Tübingen, Germany. bock@uni-tuebingen.de
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D018435:ATP Binding Cassette Transporter, Subfamily B / Q000096:biosynthesis*; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis*; D000975:Antioxidants / Q000494:pharmacology; D018938:Caco-2 Cells; D014453:Glucuronosyltransferase / Q000096:biosynthesis*; D006801:Humans; D015151:Immunoblotting; D026901:Membrane Transport Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D011794:Quercetin / Q000494:pharmacology; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists; D013723:Teratogens / Q000494:pharmacology
D018435:ATP Binding Cassette Transporter, Subfamily B; D018528:ATP-Binding Cassette Transporters; D000975:Antioxidants; D014453:Glucuronosyltransferase; D026901:Membrane Transport Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000072317:Polychlorinated Dibenzodioxins; D011794:Quercetin; D018336:Receptors, Aryl Hydrocarbon; D013723:Teratogens; C000715087:ABCC2 protein, human; C110655:UDP-glucuronosyltransferase, UGT1A6; C421109:multidrug resistance-associated protein 1