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Detergents as intrinsic P-glycoprotein substrates and inhibitors

Li-Blatter, X. and Nervi, P. and Seelig, A.. (2009) Detergents as intrinsic P-glycoprotein substrates and inhibitors. Biochimica et biophysica acta, Vol. 1788, H. 10. pp. 2335-2344.

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Official URL: http://edoc.unibas.ch/dok/A5258453

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Abstract

We assessed the interaction of three electrically neutral detergents (Triton X-100, C(12)EO(8), and Tween 80) with P-glycoprotein (ABCB1, MDR1) and identified the molecular elements responsible for this interaction. To this purpose we titrated P-glycoprotein in inside-out plasma membrane vesicles of MDR1-transfected mouse embryo fibroblasts (NIH-MDR1-G185) with the detergents below their critical micelle concentration, CMC. The P-glycoprotein ATPase measured as a function of the detergent concentration yielded bell-shaped activity curves which were evaluated with a two-site binding model. The lipid-water partition coefficient and the transporter-water binding constant of the detergents were measured independently. Knowledge of these two parameters allowed assessment of the free energy of detergent binding to P-glycoprotein in the lipid membrane, DeltaG(tl)(0), that reflects the direct detergent-transporter affinity. It increased as the number of ethoxyl groups increased, suggesting that these hydrogen bond acceptor groups are the key elements for the detergent-transporter interaction in the lipid membrane. The free energy of binding to P-glycoprotein per ethoxyl group (EO) was determined as approximately DeltaG(EO)(0)=-1.6 kJ/mol. The present findings moreover document that, depending on the concentration applied, detergents are intrinsic substrates for, or inhibitors of P-glycoprotein.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Biophysical Chemistry (Seelig A)
UniBasel Contributors:Seelig-Löffler, Anna
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Elsevier
ISSN:0006-3002
Note:Publication type according to Uni Basel Research Database: Journal article
Last Modified:22 Mar 2012 14:20
Deposited On:22 Mar 2012 13:20

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