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Mechanisms of Regulation of Amyloid-Induced Permeability of Model Lipid Membranes by Polyphenols

Abstract

This work is devoted to the study of the processes of formation and functioning of ion channels by amyloidogenic peptides, pathological aggregation and accumulation of which is a cause of neurodegenerative disorders. The effect of the plant polyphenols phloretin, butein, resveratrol, isoliquiritigenin, 4'-hydroxychalcone, and cardamonine on the pore-forming activity of β-amyloid peptide fragment 25–35 in bilayer lipid membranes from palmitoyl-phosphocholine was studied. It was demonstrated that the introduction of phloretin, butein or isoliquiritigenin in membrane-bathing solutions to a concentration of 20 µM leads to the increase of macroscopic transmembrane currents induced by peptide. At the same time, cardamonine, 4'-hydroxychalcone, and resveratrol have no effect on the activity of β-amyloid peptide fragment 25–35. The comparison of the results of studying the effect of tested polyphenols on electric and elastic properties of model membranes and pore-forming ability of β-amyloid peptide fragment 25–35 allowed it to concluded that there is no connection between the potentiating effect of phloretin, butein, or isoliquiritigenin and changes in the physicochemical properties of lipid bilayers. Results obtained by means of a confocal fluorescent microscopy indicate that the domain organization of the lipid bilayer may play a role in the pore-forming activity of amyloidogenic peptide. The results of electrophysiological measurements obtained for α-synuclein (another protein forming ion-permeable pores) do not contradict the hypothesis of binding of polyphenols, hydroxylated in the 7 position of the A cycle and in the 4'-position of the B cycle, with an open propane fragment with β-layers formed by amyloid peptides.

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ACKNOWLEDGMENTS

We are grateful to F.A. Gurnev for providing α-synuclein and discussion of the results of the work.

Funding

This work was supported in part by the Russian Foundation for Basic Research (project no. 16-04-00806) (the results on the effect of chalcones on the membrane activity of amyloidogenic peptides) and by the Russian Science Foundation (project no. 17-74-10137) (the results on the effect of polyphenols on thermotropic lipid behavior). S.S. Efimova was awarded with a scholarship of the President of the Russian Federation, SP-484.2018.4.

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Correspondence to S. S. Efimova.

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The authors declare that they have no conflict of interest. This article does not contain any studies involving animals or human participants performed by any of the a-uthors.

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Translated by A. Barkhash

   Abbreviations:25-35—β-amyloid peptide fragment 25–35, POPC—1-palmitoyl-2-oleyl-sn-glycero-3-phosphocholine, DOPC—1,2-dioleyl-sn-glycero-3-phosphocholine, DPPC—1,2-dipalmitoyl-sn-glycero-3-phosphocholine, SM—sphingomyelin from porcine brain, I—steady-state transmembrane current induced by Aβ25-35 or α-synuclein; Δφd—change in membrane dipole potential.

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Efimova, S.S., Ostroumova, O.S. Mechanisms of Regulation of Amyloid-Induced Permeability of Model Lipid Membranes by Polyphenols. Cell Tiss. Biol. 13, 312–320 (2019). https://doi.org/10.1134/S1990519X19040023

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Keywords:

  • β-amyloid peptide fragment 25–35
  • ion channels
  • butein
  • phloretin
  • lipid bilayers
  • liposomes