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An ω-3, but Not an ω-6 Polyunsaturated Fatty Acid Decreases Membrane Dipole Potential and Stimulates Endo-Lysosomal Escape of Penetratin

Although the largely positive intramembrane dipole potential (DP) may substantially influence the function of transmembrane proteins, its investigation is deeply hampered by the lack of measurement techniques suitable for high-throughput examination of living cells. Here, we describe a novel emissio...

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Autores principales: Zakany, Florina, Szabo, Mate, Batta, Gyula, Kárpáti, Levente, Mándity, István M., Fülöp, Péter, Varga, Zoltan, Panyi, Gyorgy, Nagy, Peter, Kovacs, Tamas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074792/
https://www.ncbi.nlm.nih.gov/pubmed/33912562
http://dx.doi.org/10.3389/fcell.2021.647300
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author Zakany, Florina
Szabo, Mate
Batta, Gyula
Kárpáti, Levente
Mándity, István M.
Fülöp, Péter
Varga, Zoltan
Panyi, Gyorgy
Nagy, Peter
Kovacs, Tamas
author_facet Zakany, Florina
Szabo, Mate
Batta, Gyula
Kárpáti, Levente
Mándity, István M.
Fülöp, Péter
Varga, Zoltan
Panyi, Gyorgy
Nagy, Peter
Kovacs, Tamas
author_sort Zakany, Florina
collection PubMed
description Although the largely positive intramembrane dipole potential (DP) may substantially influence the function of transmembrane proteins, its investigation is deeply hampered by the lack of measurement techniques suitable for high-throughput examination of living cells. Here, we describe a novel emission ratiometric flow cytometry method based on F66, a 3-hydroxiflavon derivative, and demonstrate that 6-ketocholestanol, cholesterol and 7-dehydrocholesterol, saturated stearic acid (SA) and ω-6 γ-linolenic acid (GLA) increase, while ω-3 α-linolenic acid (ALA) decreases the DP. These changes do not correlate with alterations in cell viability or membrane fluidity. Pretreatment with ALA counteracts, while SA or GLA enhances cholesterol-induced DP elevations. Furthermore, ALA (but not SA or GLA) increases endo-lysosomal escape of penetratin, a cell-penetrating peptide. In summary, we have developed a novel method to measure DP in large quantities of individual living cells and propose ALA as a physiological DP lowering agent facilitating cytoplasmic entry of penetratin.
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spelling pubmed-80747922021-04-27 An ω-3, but Not an ω-6 Polyunsaturated Fatty Acid Decreases Membrane Dipole Potential and Stimulates Endo-Lysosomal Escape of Penetratin Zakany, Florina Szabo, Mate Batta, Gyula Kárpáti, Levente Mándity, István M. Fülöp, Péter Varga, Zoltan Panyi, Gyorgy Nagy, Peter Kovacs, Tamas Front Cell Dev Biol Cell and Developmental Biology Although the largely positive intramembrane dipole potential (DP) may substantially influence the function of transmembrane proteins, its investigation is deeply hampered by the lack of measurement techniques suitable for high-throughput examination of living cells. Here, we describe a novel emission ratiometric flow cytometry method based on F66, a 3-hydroxiflavon derivative, and demonstrate that 6-ketocholestanol, cholesterol and 7-dehydrocholesterol, saturated stearic acid (SA) and ω-6 γ-linolenic acid (GLA) increase, while ω-3 α-linolenic acid (ALA) decreases the DP. These changes do not correlate with alterations in cell viability or membrane fluidity. Pretreatment with ALA counteracts, while SA or GLA enhances cholesterol-induced DP elevations. Furthermore, ALA (but not SA or GLA) increases endo-lysosomal escape of penetratin, a cell-penetrating peptide. In summary, we have developed a novel method to measure DP in large quantities of individual living cells and propose ALA as a physiological DP lowering agent facilitating cytoplasmic entry of penetratin. Frontiers Media S.A. 2021-04-12 /pmc/articles/PMC8074792/ /pubmed/33912562 http://dx.doi.org/10.3389/fcell.2021.647300 Text en Copyright © 2021 Zakany, Szabo, Batta, Kárpáti, Mándity, Fülöp, Varga, Panyi, Nagy and Kovacs. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Zakany, Florina
Szabo, Mate
Batta, Gyula
Kárpáti, Levente
Mándity, István M.
Fülöp, Péter
Varga, Zoltan
Panyi, Gyorgy
Nagy, Peter
Kovacs, Tamas
An ω-3, but Not an ω-6 Polyunsaturated Fatty Acid Decreases Membrane Dipole Potential and Stimulates Endo-Lysosomal Escape of Penetratin
title An ω-3, but Not an ω-6 Polyunsaturated Fatty Acid Decreases Membrane Dipole Potential and Stimulates Endo-Lysosomal Escape of Penetratin
title_full An ω-3, but Not an ω-6 Polyunsaturated Fatty Acid Decreases Membrane Dipole Potential and Stimulates Endo-Lysosomal Escape of Penetratin
title_fullStr An ω-3, but Not an ω-6 Polyunsaturated Fatty Acid Decreases Membrane Dipole Potential and Stimulates Endo-Lysosomal Escape of Penetratin
title_full_unstemmed An ω-3, but Not an ω-6 Polyunsaturated Fatty Acid Decreases Membrane Dipole Potential and Stimulates Endo-Lysosomal Escape of Penetratin
title_short An ω-3, but Not an ω-6 Polyunsaturated Fatty Acid Decreases Membrane Dipole Potential and Stimulates Endo-Lysosomal Escape of Penetratin
title_sort ω-3, but not an ω-6 polyunsaturated fatty acid decreases membrane dipole potential and stimulates endo-lysosomal escape of penetratin
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074792/
https://www.ncbi.nlm.nih.gov/pubmed/33912562
http://dx.doi.org/10.3389/fcell.2021.647300
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