Differentiation of the P-gp and MRP1 multidrug resistance systems by mobile lipid 1H-NMR spectroscopy and phosphatidylserine externalization.
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.
Mannechez
A
A
LRMBM, Faculté de Médecine, Rennes, France. amannech@univ-rennesl.fr
Collet
B
B
Payen
L
L
Lecureur
V
V
Fardel
O
O
Le Moyec
L
L
de Certaines
J D
JD
Leray
G
G
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
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