Please use this identifier to cite or link to this item: https://doi.org/10.1042/0264-6021:3610497
Title: Role of glutathione in the multidrug resistance protein 4 (MRP4/ABCC4)-mediated efflux of cAMP and resistance to purine analogues
Authors: Lai, L.
Tan, T.M.C. 
Keywords: ATP-binding cassette
Cyclic nucleotides
Glutathione S-conjugate export pump
Multispecific organic anion transporter B
Issue Date: 1-Feb-2002
Citation: Lai, L., Tan, T.M.C. (2002-02-01). Role of glutathione in the multidrug resistance protein 4 (MRP4/ABCC4)-mediated efflux of cAMP and resistance to purine analogues. Biochemical Journal 361 (3) : 497-503. ScholarBank@NUS Repository. https://doi.org/10.1042/0264-6021:3610497
Abstract: Multidrug resistance protein 4 (MRP4/ABCC4) is a member of the MRP subfamily, which in turn is a member of the superfamily of ATP-binding-cassette (ABC) transporters. Within the MRP subfamily, ABCC4, ABCC5 (MRP5), ABCC11 (MRP8) and ABCC12 (MRP9) have similar predicted membrane topologies, All lack the additional transmembrane domain, TMD0, which is present in the other MRPs. Using cells stably overexpressing ABCC4, this study shows that ABCC4 exports GSH. ABCC4 also facilitates the efflux of cAMP. Depletion of intracellular GSH with DL-buthionine-(S,R)-sulphoximine led to decreased export of cAMP and a corresponding increase in intracellular cAMP was observed. ABCC4 also mediates resistance to purine analogues 9-(2-phosphonylmethoxyethyl)-adenine and 6-thioguanine. This resistance can be reversed by the presence of DL-buthionine-(S,R)-sulphoximine. We conclude that as well as nucleotide and nucleoside analogues, ABCC4 can mediate the export of GSH. In addition, GSH plays an important role in the function of ABCC4. Depletion of intracellular GSH adversely affects the export of cAMP by ABCC4. Resistance to nucleoside analogues is also adversely affected by depletion of cellular GSH.
Source Title: Biochemical Journal
URI: http://scholarbank.nus.edu.sg/handle/10635/113635
ISSN: 02646021
DOI: 10.1042/0264-6021:3610497
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