Document Detail


Phosphatidylcholine and phosphatidylethanolamine behave as substrates of the human MDR1 P-glycoprotein.
MedLine Citation:
PMID:  9153408     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The multidrug resistant cell line CEM/VBL300 and the parental CEM T-lymphoblastic cell line from which it was derived were used to study the accumulation of fluorescent phospholipid analogs of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS). The fluorescent analogs NBD-PC, NBD-PE, and NBD-PS and [3H]PC were delivered in liposomes prepared by ethanol injection. Fluorescence microscopy demonstrated decreased accumulation of the NBD-PC analog in the multidrug resistant cell line compared to the parental cell line. Verapamil enhanced NBD-PC accumulation in the resistant cells. Similar results were obtained with insect cells expressing high levels of recombinant human MDR1. Elimination of NBD fluorescence on the outer leaflet of the plasma membrane with dithionite permitted quantification of the internal cellular fluorescence by FACS analysis. The drug resistant CEM/VBL300 cells accumulated approximately 10% the amount of NBD-PE and 20% the amount of NBD-PC compared to CEM drug sensitive cells. No difference in internal accumulation of NBD-PS was found between the drug resistant and drug sensitive cell lines. The internal accumulation of NBD-PE and NBD-PC was enhanced by the MDR reversal agents verapamil, cyclosporin A, and SDZ PSC 833 in the CEM/VBL300 cells but not in the CEM cells. The increased accumulation was dose dependent, and the relative potency of the reversal agents paralleled their ability to circumvent multidrug resistance. In addition, the monoclonal antibody UIC2 directed against the P-glycoprotein produced similar results. The evidence presented here suggests that PC and PE but not PS behave as substrates for human MDR1 P-glycoprotein.
Authors:
I Bosch; K Dunussi-Joannopoulos; R L Wu; S T Furlong; J Croop
Related Documents :
8097728 - Kinetics of cellular permeability of phenoxazine and its dependence on p-glycoprotein e...
311338 - Guinea-pig lymphotoxin resistant l-cell sublines.
19725928 - Involvement of abc transporters in melanogenesis and the development of multidrug resis...
17350618 - Effect of excess synthesis of extracellular matrix components by trabecular meshwork ce...
3403538 - Regulation of ornithine decarboxylase and other cell cycle-dependent genes during senes...
17383428 - Suppression of fhl2 expression induces cell differentiation and inhibits gastric and co...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Biochemistry     Volume:  36     ISSN:  0006-2960     ISO Abbreviation:  Biochemistry     Publication Date:  1997 May 
Date Detail:
Created Date:  1997-06-09     Completed Date:  1997-06-09     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  5685-94     Citation Subset:  IM    
Affiliation:
Dana-Farber Cancer Institute, Division of Pediatric Hematology/Oncology, Boston, Massachusetts 02115, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
4-Chloro-7-nitrobenzofurazan / analogs & derivatives,  metabolism
Drug Resistance, Multiple*
Fluorescent Dyes
Humans
Leukemia, T-Cell / metabolism
Microscopy, Fluorescence
P-Glycoprotein / biosynthesis,  metabolism*
Phosphatidylcholines / metabolism*
Phosphatidylethanolamines / metabolism*
Phospholipids / metabolism
Substrate Specificity
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
AI24570/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/1-acyl-2-(12-((7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)dodecanoyl)phosphatidylcholine; 0/Fluorescent Dyes; 0/P-Glycoprotein; 0/Phosphatidylcholines; 0/Phosphatidylethanolamines; 0/Phospholipids; 10199-89-0/4-Chloro-7-nitrobenzofurazan; 64205-19-2/N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)phosphatidylethanolamine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Insufficiency of self-phosphorylation for the activation of epidermal growth factor receptor.
Next Document:  Lipid bilayer electrostatic energy, curvature stress, and assembly of gramicidin channels.