H. Alex Brown
Principle Investigator; Professor of Pharmacology, Chemistry, and Biochemistry; Associate Director, VICB;
Last active: 2/12/2015

Long term myriocin treatment increases MRP1 transport activity.

Meszaros P, Klappe K, van Dam A, Ivanova PT, Milne SB, Myers DS, Brown HA, Permentier H, Hoekstra D, Kok JW
Int J Biochem Cell Biol. 2013 45 (2): 326-34

PMID: 23178537 · PMCID: PMC3826170 · DOI:10.1016/j.biocel.2012.11.009

We investigated the effect of myriocin treatment, which extensively depletes sphingolipids from cells, on multidrug resistance-related protein 1 (MRP1) efflux activity in MRP1 expressing cells and isolated plasma membrane vesicles. Our data reveal that both short term (3 days) and long term (7 days) treatment effectively reduce the cellular sphingolipid content to the same level. Intriguingly, a two-fold increase in MRP1-mediated efflux activity was observed following long term treatment, while short term treatment had no impact. Very similar data were obtained with plasma membrane vesicles isolated from myriocin-treated cells. Exploiting the cell-free vesicle system, Michaelis-Menten analysis revealed that the intrinsic MRP1 activity remained unaltered; however, the fraction of active transporter molecules increased. We demonstrate that the latter effect is due to an enhanced recruitment of MRP1 into lipid raft fractions, thereby promoting MRP1 activity.

Copyright © 2012 Elsevier Ltd. All rights reserved.

MeSH Terms (15)

Adenosine Triphosphatases Animals Caveolins Cricetinae Fatty Acids, Monounsaturated Humans Kinetics Leukotriene C4 Membrane Microdomains Mice Multidrug Resistance-Associated Proteins NIH 3T3 Cells Phosphatidylserines Protein Transport Sphingolipids

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