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Title: Effects of plant polyphenols and mutational analysis of multidrug resistance protein 4 (MRP4/ABCC4) functions
Authors: WU JUAN
Keywords: multidrug resistance protein4,bimane-glutathione,glutathione,plant polyphenols and flavonoids,site-directed mutagenesis,single-nucleotide polymorphism
Issue Date: 9-Sep-2005
Citation: WU JUAN (2005-09-09). Effects of plant polyphenols and mutational analysis of multidrug resistance protein 4 (MRP4/ABCC4) functions. ScholarBank@NUS Repository.
Abstract: Multidrug resistance protein 4 (MRP4/ABCC4) is a member of the ATP-binding cassette transport superfamily. MRP4 contributes to the resistance to a variety of chemotherapeutic agents and the transport of structurally diverse conjugated organic anions, including glutathione-S-conjugates. Using cells stably overexpressing MRP4, this study confirmed that MRP4 can facilitate the efflux of the glutathione conjugate, bimane-glutathione. This transport can be modulated by certain plant polyphenols, including ellagic acid, curcumin, and the flavonoids apigenin, kaempferol and luteolin.This study also confirmed that MRP4 is able to facilitate glutathione efflux. The efflux can be also modulated by plant polyphenols and flavonoids, including ellagic acid, curcumin, apigenin, kaempferol, luteolin, genistein and quercetin. In addition, our study demonstrated that conserved charged amino acid residue Arg165 and the single-nucleotide polymorphism (SNP) site Cys171Gly are important determinants for MRP4-mediated transport of bimane-glutathione, glutathione and resistance to purine analogues 6-TG and 6-MP.
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