title: Interactions of retinoids with the ABC transporters P-glycoprotein and Breast Cancer Resistance Protein.
abstract: Retinoids - derivatives of vitamin A - are important cell permeant signaling molecules that regulate gene expression through activation of nuclear receptors. P-glycoprotein (Pgp) and ABCG2 are plasma membrane efflux transporters affecting the tissue distribution of numerous structurally unrelated lipophilic compounds. In the present work we aimed to study the interaction of the above ABC transporters with retinoid derivatives. We have found that 13-cis-retinoic acid, retinol and retinyl-acetate inhibited the Pgp and ABCG2 mediated substrate transport as well as the substrate stimulated ATPase activity of these transporters. Interestingly, 9-cis-retinoic acid and ATRA (all-trans retinoic acid), both are stereoisomers of 13-cis-retinoic acid, did not have any effect on the transporters' activity. Our fluorescence anisotropy measurements revealed that 13-cis-retinoic acid, retinol and retinyl-acetate selectively increase the viscosity and packing density of the membrane. Thus, the mixed-type inhibition of both transporters by retinol and ABCG2 by 13-cis-retinoic acid may be the collective result of direct interactions of these retinoids with the substrate binding site(s) and of indirect interactions mediated by their membrane rigidifying effects.
authors.affiliation: Department of Biophysics and Cell Biology, University of Debrecen, Debrecen, H-4002 Egyetem tér 1, P.O.B. 400, Hungary.
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Tarapcsák
authors.affiliation: Department of Biophysics and Cell Biology, University of Debrecen, Debrecen, H-4002 Egyetem tér 1, P.O.B. 400, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Szalóki
authors.affiliation: Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, H-1117 Magyar tudósok körútja 2, P.O.B. 286, Hungary.
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Telbisz
authors.affiliation: Department of Biophysics and Cell Biology, University of Debrecen, Debrecen, H-4002 Egyetem tér 1, P.O.B. 400, Hungary.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Gyöngy
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Debrecen, Debrecen, H-4002 Egyetem tér 1, P.O.B. 400, Hungary.
authors.forename: Krisztina
authors.initials: K
authors.lastname: Matúz
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Debrecen, Debrecen, H-4002 Egyetem tér 1, P.O.B. 400, Hungary.
authors.forename: Éva
authors.initials: É
authors.lastname: Csősz
authors.affiliation: Department of Biophysics and Cell Biology, University of Debrecen, Debrecen, H-4002 Egyetem tér 1, P.O.B. 400, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Nagy
authors.affiliation: Institute of Horticulture, University of Debrecen, Debrecen, H-4015 Böszörményi út 138, P.O.B. 400, Hungary.|Plant Protection Institute, Centre for Agricultural Research, Hungarian Academy of Sciences, Budapest, H-1525 Hermann Ottó út 15, P.O.B. 525, Hungary.
authors.forename: Imre J
authors.initials: IJ
authors.lastname: Holb
authors.affiliation: MTA-DE, Public Health Research Group of the Hungarian Academy of Sciences, Faculty of Public Health, University of Debrecen, Debrecen, H-4028 Kassai út 26, P.O.B. 400, Hungary.
authors.forename: Ralph
authors.initials: R
authors.lastname: Rühl
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Debrecen, Debrecen, H-4002 Egyetem tér 1, P.O.B. 400, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Nagy
authors.affiliation: Department of Biophysics and Cell Biology, University of Debrecen, Debrecen, H-4002 Egyetem tér 1, P.O.B. 400, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Szabó
authors.affiliation: Department of Biophysics and Cell Biology, University of Debrecen, Debrecen, H-4002 Egyetem tér 1, P.O.B. 400, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Goda
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D004285:Dogs; D005454:Fluorescence Polarization; D006801:Humans; D007700:Kinetics; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D041681:NIH 3T3 Cells; D009363:Neoplasm Proteins / Q000378:metabolism*; D012176:Retinoids / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: C116614:ABCG2 protein, human; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D009363:Neoplasm Proteins; D012176:Retinoids; D000251:Adenosine Triphosphatases