Veterinärmedizinische Universität Wien Forschungsinformationssystem VetDoc

Gewählte Publikation:

Open Access Logo

Publikationstyp: Zeitschriftenaufsatz
Dokumenttyp: Originalarbeit

Jahr: 2019

AutorInnen: Jovanović, O; Škulj, S; Pohl, EE; Vazdar, M

Titel: Covalent modification of phosphatidylethanolamine by 4-hydroxy-2-nonenal increases sodium permeability across phospholipid bilayer membranes.

Quelle: Free Radic Biol Med. 2019; 143:433-440



Autor/innen der Vetmeduni Vienna:

Jovanovic Olga
Pohl Elena

Beteiligte Vetmed-Organisationseinheiten
Institut für Physiologie, Pathophysiologie und Biophysik, Abteilung für Physiologie und Biophysik


Zugehörige(s) Projekt(e): Mechanismus der UCP-Aktivierung durch reaktive Aldehyde


Abstract:
Reactive aldehydes (RAs), such as 4-hydroxy-2-nonenal (HNE) and 4-oxo-2-nonenal (ONE), produced by cells under conditions of oxidative stress, were shown to react with phosphatidylethanolamine (PE) in biological and artificial membranes. They form RA-PE adducts, which affect the function of membrane proteins by modifying various biophysical properties of the membrane. The ratio of protein to lipid in biological membranes is different, but can reach 0.25 in the membranes of oligodendrocytes. However, the impact of RA-PE adducts on permeability (P) of the neat lipid phase and molecular mechanism of their action are poorly understood. In this study, we showed that HNE increased the membrane P for ions, and in particular for sodium. This effect depended on the presence of DOPE, and was not recorded for the more toxic compound, ONE. Molecular dynamics simulations suggested that HNE-PE and ONE-PE adducts anchored different positions in the lipid bilayer, and thus changed the membrane lipid area and bilayer thickness in different ways. Sodium permeability, calculated in the presence of double HNE-PE adducts, was increased by three to four orders of magnitude when compared to PNa in adduct - free membranes. A novel mechanism by which HNE alters permeability of the lipid membrane may explain the multiple toxic or regulative effects of HNE on the function of excitable cells, such as neurons, cardiomyocytes and neurosensory cells under conditions of oxidative stress.Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

Keywords Pubmed: Aldehydeschemistry
Cell Membranemetabolism
Cell Membrane Permeability
Humans
Lipid Bilayersmetabolism
Lipid Peroxidation
Molecular Dynamics Simulation
Oxidative Stress
Phosphatidylethanolamineschemistry
Sodiummetabolism

© Veterinärmedizinische Universität Wien Hilfe und DownloadsErklärung zur Barrierefreiheit