The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Susan P C Cole - One of the best experts on this subject based on the ideXlab platform.
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Multidrug Resistance protein 1 mrp1 abcc1 a multitasking atp binding cassette abc transporter
Journal of Biological Chemistry, 2014Co-Authors: Susan P C ColeAbstract:The Multidrug Resistance protein 1 (MRP1) encoded by ABCC1 was originally discovered as a cause of Multidrug Resistance in tumor cells. However, it is now clear that MRP1 serves a broader role than simply mediating the ATP-dependent efflux of drugs from cells. The antioxidant GSH and the pro-inflammatory cysteinyl leukotriene C4 have been identified as key physiological organic anions effluxed by MRP1, and an ever growing body of evidence indicates that additional lipid-derived mediators are also substrates of this transporter. As such, MRP1 is a multitasking transporter that likely influences the etiology and progression of a host of human diseases.
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transmembrane transport of endo and xenobiotics by mammalian atp binding cassette Multidrug Resistance proteins
Physical Review, 2006Co-Authors: Roger G Deeley, Christopher J Westlake, Susan P C ColeAbstract:Multidrug Resistance Proteins (MRPs), together with the cystic fibrosis conductance regulator (CFTR/ABCC7) and the sulfonylurea receptors (SUR1/ABCC8 and SUR2/ABCC9) comprise the 13 members of the ...
Piet Borst - One of the best experts on this subject based on the ideXlab platform.
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the Multidrug Resistance protein family
Biochimica et Biophysica Acta, 1999Co-Authors: Piet Borst, Raymond Evers, Marcel Kool, Jan WijnholdsAbstract:Abstract The human Multidrug Resistance protein (MRP) family contains at least six members: MRP1, the godfather of the family and well known as the Multidrug Resistance protein, and five homologs, called MRP2–6. In this review, we summarize what is known about the protein structure, the expression in tissues, the routing in cells, the physiological functions, the substrate specificity, and the role in Multidrug Resistance of the individual members of the MRP family.
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transport of the glutathione conjugate of ethacrynic acid by the human Multidrug Resistance protein mrp
FEBS Letters, 1996Co-Authors: Guido J R Zaman, Nicole H P Cnubben, Peter J Van Bladeren, Raymond Evers, Piet BorstAbstract:The Multidrug Resistance protein MRP has been shown to mediate the transport of glutathione S-conjugates across membranes. In this study we demonstrate that the glutathione S-conjugate of the diuretic drug ethacrynic acid, which is an efficient inhibitor of glutathione S-transferases, is a high-affinity substrate and inhibitor of the glutathione S-conjugate pump associated with MRP. This implies that ethacrynic acid may modulate drug Resistance of tumor cells not only by inhibiting glutathione S-transferase activity, but also by inhibiting the export of drug conjugates from the cell by MRP. Chemicals/CAS: Adenosine Monophosphate, 61-19-8; ATP-Binding Cassette Transporters; Ethacrynic Acid, 58-54-8; Glutathione, 70-18-8; Multidrug Resistance-Associated Proteins; Recombinant Proteins; Sulfinpyrazone, 57-96-5
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overexpression of the gene encoding the Multidrug Resistance associated protein results in increased atp dependent glutathione s conjugate transport
Proceedings of the National Academy of Sciences of the United States of America, 1994Co-Authors: Michael Muller, Guido J R Zaman, Piet Borst, C J L M Meijer, R J Scheper, N H Mulder, E G E De Vries, Peter L M JansenAbstract:The Multidrug Resistance-associated protein (MRP) is a 180- to 195-kDa glycoprotein associated with Multidrug Resistance of human tumor cells. MRP is mainly located in the plasma membrane and it confers Resistance by exporting natural product drugs out of the cell. Here we demonstrate that overexpression of the MRP gene in human cancer cells increases the ATP-dependent glutathione S-conjugate carrier activity in plasma membrane vesicles isolated from these cells. The glutathione S-conjugate export carrier is known to mediate excretion of bivalent anionic conjugates from mammalian cells and is thought to play a role in the elimination of conjugated xenobiotics. Our results suggest that MRP can cause Multidrug Resistance by promoting the export of drug modification products from cells and they shed light on the reported link between drug Resistance and cellular glutathione and glutathione S-transferase levels.
Jan Wijnholds - One of the best experts on this subject based on the ideXlab platform.
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Multidrug Resistance protein 5 is a multispecific organic anion transporter able to transport nucleotide analogs
Proceedings of the National Academy of Sciences of the United States of America, 2000Co-Authors: Jan Wijnholds, Jos H Beijnen, C A A M Mol, Liesbeth Van Deemter, Marcel De Haas, George L Scheffer, Frank Baas, Rik J Scheper, Sigrid Hatse, Erik De ClercqAbstract:Two prominent members of the ATP-binding cassette superfamily of transmembrane proteins, Multidrug Resistance 1 (MDR1) P-glycoprotein and Multidrug Resistance protein 1 (MRP1), can mediate the cellular extrusion of xenobiotics and (anticancer) drugs from normal and tumor cells. The MRP subfamily consists of at least six members, and here we report the functional characterization of human MRP5. We found Resistance against the thiopurine anticancer drugs, 6-mercaptopurine (6-MP) and thioguanine, and the anti-HIV drug 9-(2-phosphonylmethoxyethyl)adenine (PMEA) in MRP5-transfected cells. This Resistance is due to an increased extrusion of PMEA and 6-thioinosine monophosphate from the cells that overproduce MRP5. In polarized Madin–Darby canine kidney II (MDCKII) cells transfected with an MRP5 cDNA construct, MRP5 is routed to the basolateral membrane and these cells transport S-(2,4-dinitrophenyl)glutathione and glutathione preferentially toward the basal compartment. Inhibitors of organic anion transport inhibit transport mediated by MRP5. We speculate that MRP5 might play a role in some cases of unexplained Resistance to thiopurines in acute lymphoblastic leukemia and/or to antiretroviral nucleoside analogs in HIV-infected patients.
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the Multidrug Resistance protein family
Biochimica et Biophysica Acta, 1999Co-Authors: Piet Borst, Raymond Evers, Marcel Kool, Jan WijnholdsAbstract:Abstract The human Multidrug Resistance protein (MRP) family contains at least six members: MRP1, the godfather of the family and well known as the Multidrug Resistance protein, and five homologs, called MRP2–6. In this review, we summarize what is known about the protein structure, the expression in tissues, the routing in cells, the physiological functions, the substrate specificity, and the role in Multidrug Resistance of the individual members of the MRP family.
Laura J V Piddock - One of the best experts on this subject based on the ideXlab platform.
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Multidrug-Resistance efflux pumps - Not just for Resistance
Nature Reviews Microbiology, 2006Co-Authors: Laura J V PiddockAbstract:It is well established that Multidrug-Resistance efflux pumps encoded by bacteria can confer clinically relevant Resistance to antibiotics. It is now understood that these efflux pumps also have a physiological role(s). They can confer Resistance to natural substances produced by the host, including bile, hormones and host-defence molecules. In addition, some efflux pumps of the Resistance nodulation division (RND) family have been shown to have a role in the colonization and the persistence of bacteria in the host. Here, I present the accumulating evidence that Multidrug-Resistance efflux pumps have roles in bacterial pathogenicity and propose that these pumps therefore have greater clinical relevance than is usually attributed to them.
Jue Chen - One of the best experts on this subject based on the ideXlab platform.
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structural basis of substrate recognition by the Multidrug Resistance protein mrp1
Cell, 2017Co-Authors: Zachary Lee Johnson, Jue ChenAbstract:The Multidrug Resistance protein MRP1 is an ATP-binding cassette (ABC) transporter that confers Resistance to many anticancer drugs and plays a role in the disposition and efficacy of several opiates, antidepressants, statins, and antibiotics. In addition, MRP1 regulates redox homeostasis, inflammation, and hormone secretion. Using electron cryomicroscopy, we determined the molecular structures of bovine MRP1 in two conformations: an apo form at 3.5 A without any added substrate and a complex form at 3.3 A with one of its physiological substrates, leukotriene C4. These structures show that by forming a single bipartite binding site, MRP1 can recognize a spectrum of substrates with different chemical structures. We also observed large conformational changes induced by leukotriene C4, explaining how substrate binding primes the transporter for ATP hydrolysis. Structural comparison of MRP1 and P-glycoprotein advances our understanding of the common and unique properties of these two important molecules in Multidrug Resistance to chemotherapy.