Sensitivity of taurine uptake to oxygen-derived reactive substances in MDR and non-MDR cells.
In human KB and LoVo cell lines, high affinity taurine uptake was strongly reduced in both a time and dose-dependent manner by cumene hydroperoxide (CH) and to a lesser extent by hydrogen peroxide (H2O2). Uptake-inhibition was greater in multidrug resistant (MDR) cells than in their non-MDR counterparts. Basal taurine efflux was unaffected by the oxidants. Lipid peroxidation levels closely correlated with the uptake inhibition levels, and were greater in MDR cells than in their non-MDR counterparts. The two oxidants reduced the Vmax and, to a lesser extent, the affinity of the transporter for taurine. They also reduced low affinity taurine uptake and, to a lesser extent, taurine diffusion. The composition of the medium used for cell treatment, especially its pyruvate content, greatly affected the H2O2 effect. H2O2- or CH-induced reduction of the high affinity taurine uptake was unaffected by protein kinase C (PKC) inhibitors and by the calmodulin antagonist W-13, ruling out the involvement of PKC and perhaps of calmodulin kinases in their effect.
Wersinger
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UPR 9003 du CNRS, Institut de Recherche Contre les Cancers de I'Appareil Digestif, Hĵpitaux Universitaires, Strasbourg, France.
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D001555:Benzene Derivatives / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002021:Buffers; D002147:Calmodulin / Q000037:antagonists & inhibitors; D018432:Drug Resistance, Multiple; D005609:Free Radicals / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007624:KB Cells; D015227:Lipid Peroxidation; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D019289:Pyruvic Acid / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D013654:Taurine / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D001555:Benzene Derivatives; D002021:Buffers; D002147:Calmodulin; D005609:Free Radicals; D016877:Oxidants; D017382:Reactive Oxygen Species; D013654:Taurine; D019289:Pyruvic Acid; D006861:Hydrogen Peroxide; D011493:Protein Kinase C; C007164:cumene hydroperoxide