Multidrug resistance‐associated proteins: Export pumps for conjugates with glutathione, glucuronate or sulfate

@article{Homolya2003MultidrugRP,
  title={Multidrug resistance‐associated proteins: Export pumps for conjugates with glutathione, glucuronate or sulfate},
  author={L{\'a}szl{\'o} Homolya and Andr{\'a}s V{\'a}radi and Bal{\'a}zs Sarkadi},
  journal={BioFactors},
  year={2003},
  volume={17}
}
Many endogenous or xenobiotic lipophilic substances are eliminated from the cells by the sequence of oxidation, conjugation to an anionic group (glutathione, glucuronate or sulfate) and transport across the plasma membrane into the extracellular space. The latter step is mediated by integral membrane glycoproteins belonging to the superfamily of ATP‐Binding Cassette (ABC) transporters. A subfamily, referred as ABCC, includes the famous/infamous cystic fibrosis transmembrane regulator (CFTR… Expand
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References

SHOWING 1-10 OF 51 REFERENCES
Conjugate export pumps of the multidrug resistance protein (MRP) family: localization, substrate specificity, and MRP2-mediated drug resistance.
TLDR
Because of its function in the terminal excretion of cytotoxic and carcinogenic substances, MRP2 as well as other members of the MRP family, play an important role in detoxification and chemoprevention. Expand
Export pumps for glutathione S-conjugates.
  • D. Keppler
  • Medicine, Chemistry
  • Free radical biology & medicine
  • 1999
TLDR
Proteins of the MRP family are indispensable for transport of glutathione S-conjugates and glutathion disulfide into the extracellular space and play a decisive role in detoxification and defense against oxidative stress. Expand
Transport of glutathione, glucuronate, and sulfate conjugates by the MRP gene-encoded conjugate export pump.
TLDR
It is established that MRP functions as an ATP-dependent export pump not only for glutathione conjugates but also for glucuronidated and sulfated endogenous as well as exogenous compounds. Expand
ATP-dependent transport of aflatoxin B1 and its glutathione conjugates by the product of the multidrug resistance protein (MRP) gene.
TLDR
It is demonstrated that MRP is capable of energy-dependent transport of aflatoxin B1 and its GSH conjugates and suggest a potential protective role for MRP in mammalian chemical carcinogenesis. Expand
A family of drug transporters: the multidrug resistance-associated proteins.
TLDR
Whether long-term inhibition of MRPs in humans can be tolerated (assuming that suitable inhibitors will be found) remains to be determined. Expand
Multidrug-resistance protein 5 is a multispecific organic anion transporter able to transport nucleotide analogs.
  • J. Wijnholds, C. Mol, +9 authors P. Borst
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 2000
TLDR
It is speculated 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. Expand
Characterization of the human multidrug resistance protein isoform MRP3 localized to the basolateral hepatocyte membrane
TLDR
The results indicate that the basolateral MRP isoform, MRP3, may be upregulated when the canalicular secretion of anionic conjugates by MRP2 is impaired. Expand
MRP3, an organic anion transporter able to transport anti-cancer drugs.
TLDR
MRP3 is an organic anion and multidrug transporter, like the GS-X pumps MRP1 and MRP2, and in Madin-Darby canine kidney II cells, MRP3 routes to the basolateral membrane and mediates transport of the organicAnion S-(2,4-dinitrophenyl-)glutathione toward the basoliateral side of the monolayer. Expand
Overexpression of the gene encoding the multidrug resistance-associated protein results in increased ATP-dependent glutathione S-conjugate transport.
  • M. Müller, C. Meijer, +5 authors P. Jansen
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1994
TLDR
It is demonstrated 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, suggesting that MRP can cause multidrug resistance by promoting the export of drug modification products from cells. Expand
FROM VACUOLAR GS-X PUMPS TO MULTISPECIFIC ABC TRANSPORTERS.
TLDR
The identification of the MRPs and the demonstration of a central role for ABC transporters, in general, in plant function not only provide fresh insights into the molecular basis of energy-dependent solute transport but also offer the prospect for manipulating and investigating many fundamental processes that have hitherto evaded analysis at the transport level. Expand
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