title: Differentiation of the P-gp and MRP1 multidrug resistance systems by mobile lipid 1H-NMR spectroscopy and phosphatidylserine externalization.
abstract: We have previously demonstrated that proton NMR spectra of fatty acid chains in erythroleukemia K562 wild-type cells and their MDR1 counterparts show variations related to the phenotype over-expressing the P-glycoprotein (P-gp). Human lung cancer cells whose multidrug resistance (MDR) counterparts over-express the multidrug resistance-associated protein MRP1 have not yet been studied by NMR. Both P-gp and MRP1 belong to the same ATP-binding cassette transporter superfamily. A comparison of NMR spectra from both these multidrug-resistance phenotypes showed that the results previously obtained on the MDR1 family are not valid for MRP1. Furthermore, flow cytofluorimetry studies with external phosphatidylserine labelling showed that P-gp and MRP1 overexpressions have strong but differentiated effects on cell lipid pools.
authors.affiliation: LRMBM, Faculté de Médecine, Rennes, France. amannech@univ-rennesl.fr
authors.forename: A
authors.initials: A
authors.lastname: Mannechez
authors.forename: B
authors.initials: B
authors.lastname: Collet
authors.forename: L
authors.initials: L
authors.lastname: Payen
authors.forename: V
authors.initials: V
authors.lastname: Lecureur
authors.forename: O
authors.initials: O
authors.lastname: Fardel
authors.forename: L
authors.initials: L
authors.lastname: Le Moyec
authors.forename: J D
authors.initials: JD
authors.lastname: de Certaines
authors.forename: G
authors.initials: G
authors.lastname: Leray
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D018288:Carcinoma, Small Cell / Q000378:metabolism / Q000473:pathology; D018432:Drug Resistance, Multiple / Q000502:physiology*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D020014:K562 Cells / Q000166:cytology / Q000378:metabolism; D050356:Lipid Metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis*; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D010718:Phosphatidylserines / Q000378:metabolism*; D011522:Protons
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010718:Phosphatidylserines; D011522:Protons; C421109:multidrug resistance-associated protein 1