These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Interaction of P-glycoprotein with defined phospholipid bilayers: a differential scanning calorimetric study.
    Author: Romsicki Y, Sharom FJ.
    Journal: Biochemistry; 1997 Aug 12; 36(32):9807-15. PubMed ID: 9245413.
    Abstract:
    One of the major causes of multidrug resistance in human cancers is expression of the P-glycoprotein multidrug transporter, which acts as a drug efflux pump. P-Glycoprotein is a member of the ABC superfamily of membrane proteins, and is composed of 12 hydrophobic membrane-spanning segments and 2 cytoplasmic nucleotide binding domains. Membrane lipids are known to play an important role in the function of P-glycoprotein. In the present study, purified P-glycoprotein of high specific ATPase activity was reconstituted into defined bilayers of dimyristoylphosphatidylcholine (DMPC), and its effects on lipid thermodynamic properties were then investigated using differential scanning calorimetry. P-Glycoprotein had a large perturbing effect on DMPC bilayers, even at relatively high lipid:protein ratios. The gel to liquid-crystalline phase transition temperature, Tm, was lowered on inclusion of P-glycoprotein in the bilayer, and the cooperativity of the transition was markedly reduced. The phase transition enthalpy, DeltaH, declined in a linear fashion with increasing P-glycoprotein content for lipid:protein ratios between 63:1 and 16:1 (w/w). Evaluation of these data using two different analytical methods indicated that P-glycoprotein perturbed either 375 or 485 phospholipids, withdrawing them from the phase transition. The DeltaH value for those lipids undergoing melting was similar to that of pure DMPC, which implies that their thermodynamic properties are essentially unchanged in the presence of P-glycoprotein. At lipid:protein ratios below 16:1 (w/w), transition enthalpy increased with higher P-glycoprotein content, until the DeltaH value reached that of pure DMPC. However, the lipid remained highly perturbed, as indicated by a very broad phase transition peak. This behavior may arise from either aggregation/oligomerization of P-glycoprotein within the bilayer or changes in the interaction of the transporter with the membrane at high density.
    [Abstract] [Full Text] [Related] [New Search]