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      Cyclosporin A in Membrane Lipids Environment: Implications for Antimalarial Activity of the Drug—The Langmuir Monolayer Studies

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          Abstract

          Cyclosporin A (CsA), a hydrophobic cyclic peptide produced by the fungus Tolypocladium inflatum, is well known for its high efficiency as an immunosuppressor for transplanted organs and anti-inflammatory properties; however, it is also active as antiparasitic (antimalarial) drug. Antimalarial mechanism of CsA action lacks a detailed understanding at molecular level. Due to a high lipophilicity of CsA, it is able to interact with lipids of cellular membrane; however, molecular targets of this drug are still unknown. To get a deeper insight into the mode of antimalarial activity of CsA, it is of utmost importance to examine its interactions with membrane components. To reach this goal, the Langmuir monolayer technique, which serves as a very useful, easy to handle and controllable model of biomembranes, has been employed. In this work, the interactions between CsA and main membrane lipids, i.e., cholesterol (Chol), 2-oleoyl-1-palmitoyl-3-phosphocholine (POPC), and sphingomyelin (SM), have been investigated. Attractive interactions are observed only for CsA mixtures with SM, while repulsive forces occur in systems containing remaining membrane lipids. Taking into consideration mutual interactions between membrane lipids (Chol–SM; Chol–POPC and SM–POPC), the behavior of CsA in model erythrocyte membrane of normal and infected cells has been analyzed. Our results prove strong affinity of CsA to SM in membrane environment. Since normal and parasitized erythrocytes differ significantly in the level of SM, this phospholipid may be considered as a molecular target for antimalarial activity of CsA.

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          The online version of this article (doi:10.1007/s00232-015-9814-9) contains supplementary material, which is available to authorized users.

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          Most cited references63

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          Cholesterol interactions with phospholipids in membranes.

          Mammalian cell membranes are composed of a complex array of glycerophospholipids and sphingolipids that vary in head-group and acyl-chain composition. In a given cell type, membrane phospholipids may amount to more than a thousand molecular species. The complexity of phospholipid and sphingolipid structures is most likely a consequence of their diverse roles in membrane dynamics, protein regulation, signal transduction and secretion. This review is mainly focused on two of the major classes of membrane phospholipids in eukaryotic organisms, sphingomyelins and phosphatidylcholines. These phospholipid classes constitute more than 50% of membrane phospholipids. Cholesterol is most likely to associate with these lipids in the membranes of the cells. We discuss the synthesis and distribution in the cell of these lipids, how they are believed to interact with each other, and what cellular consequences such interactions may have. We also include a discussion about findings in the recent literature regarding cholesterol/phospholipid interactions in model membrane systems. Finally, we look at the recent trends in computer and molecular dynamics simulations regarding phospholipid and cholesterol/phospholipid behavior in bilayer membranes.
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            • Record: found
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            • Article: not found

            Intermolecular and Surface Forces

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              • Record: found
              • Abstract: found
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              Lipid monolayers: why use half a membrane to characterize protein-membrane interactions?

              H BROCKMAN (1999)
              Variants of membrane-active proteins and peptides are increasingly available through synthesis and molecular engineering. When determining the effects of structural changes upon the interaction of these proteins with lipid membranes, monomolecular films of lipids at the air-water interface have significant advantages over bilayers and other lipid dispersions. In the past year, a variety of protein-lipid interactions has been characterized successfully using relatively simple surface measurements.
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                Author and article information

                Contributors
                ucdynaro@cyf-kr.edu.pl
                Journal
                J Membr Biol
                J. Membr. Biol
                The Journal of Membrane Biology
                Springer US (New York )
                0022-2631
                1432-1424
                16 June 2015
                16 June 2015
                2015
                : 248
                : 6
                : 1021-1032
                Affiliations
                [ ]Department of General Chemistry, Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Kraków, Poland
                [ ]Institute of Physics, Jagiellonian University, Łojasiewicza 11, 30-348 Kraków, Poland
                Article
                9814
                10.1007/s00232-015-9814-9
                4611017
                26077844
                79364491-9ab3-4ba6-b3b2-44b082601cfc
                © The Author(s) 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 26 February 2015
                : 6 June 2015
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                © Springer Science+Business Media New York 2015

                Molecular biology
                cyclosporin a,interactions,membrane lipids,langmuir monolayers,model of normal and parasitized erythrocyte membrane

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