PMID: 9187270Jun 1, 1997Paper

ATP-dependent transport of aflatoxin B1 and its glutathione conjugates by the product of the multidrug resistance protein (MRP) gene

Molecular Pharmacology
D W LoeS P Cole

Abstract

Glutathione-S-transferase-catalyzed conjugation of glutathione (GSH) to aflatoxin B1-8,9-epoxide plays an important role in preventing binding of this ultimate carcinogen to target macromolecules. Once formed, the aflatoxin B1-epoxide-GSH conjugates are actively extruded from the cell by an unidentified ATP-dependent export pump or pumps. Two possible candidates for this GSH conjugate pump are the 190-kDa multidrug resistance protein (MRP) and the 170-kDa P-glycoprotein. Both proteins belong to the ATP-binding cassette superfamily of transmembrane transport proteins and confer resistance to a similar spectrum of natural-product drugs. Using membrane vesicles from MRP-transfected cells, we found that MRP transports GSH conjugates of both the endo-isomers and exo-isomers of aflatoxin B1-8,9-epoxide in an ATP-dependent, osmotically sensitive manner (V(max) = 180 pmol/mg/min, K(m) = 189 nM). Membrane vesicles from P-glycoprotein-overexpressing cells showed very low levels of transport. MRP-mediated transport was inhibited by an MRP-specific monoclonal antibody and by a variety of GSH derivatives and cholestatic steroid glucuronides. ATP-dependent transport of unmodified aflatoxin B1 by MRP-enriched membrane vesicles was low but mar...Continue Reading

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Citations

Jan 23, 2003·The Journal of Pharmacology and Experimental Therapeutics·Elaine M LeslieSusan P C Cole
Dec 20, 2003·Pharmacogenomics·Toshihisa IshikawaYasuhiro Sumino
Jun 22, 2005·Respiratory Research·Margaretha van der DeenDirkje S Postma
Mar 15, 2011·Cancer Chemotherapy and Pharmacology·Howard R Mellor, Richard Callaghan
Mar 29, 2014·American Journal of Therapeutics·Darryl R PetersonDemetrios Zikos
Mar 29, 2014·Drug Metabolism Reviews·Tereza Kunická, Pavel Souček
Mar 4, 2015·Journal of Experimental Botany·Stephanie WalterFiona M Doohan
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Nov 4, 2016·Pharmaceutical Research·Anand A JoshiPhillip M Gerk
Jul 18, 2003·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Kenichi NunoyaRoger G Deeley
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Mar 24, 2006·Nephron. Physiology·Vincent Launay-VacherGilbert Deray

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