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: A Mannechez, B Collet, L Payen, V Lecureur, O Fardel, L Le Moyec, J D de Certaines, G Leray
• Journal: Anticancer research (Anticancer Res) 2001 Nov-Dec Vol. 21 Issue 6A Pg. 3915-9 ISSN: 0250-7005 [Print] Greece
• PMID: 11911269 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Multidrug Resistance-Associated Proteins
• Phosphatidylserines
• Protons
• multidrug resistance-associated protein 1

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (biosynthesis)
• Carcinoma, Small Cell (metabolism, pathology)
• Drug Resistance, Multiple (physiology)
• Drug Resistance, Neoplasm
• Humans
• K562 Cells (cytology, metabolism)
• Lipid Metabolism
• Lung Neoplasms (metabolism, pathology)
• Multidrug Resistance-Associated Proteins (biosynthesis)
• Nuclear Magnetic Resonance, Biomolecular (methods)
• Phosphatidylserines (metabolism)
• Protons