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

Jovanović, Olga; Škulj, Sanja; Pohl, Elena E.; Vazdar, Mario (2019) Covalent modification of phosphatidylethanolamine by 4-hydroxy-2-nonenal increases sodium permeability across phospholipid bilayer membranes. Free Radical Biology and Medicine, 143 . pp. 433-440. ISSN 0891-5849

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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.

Item Type: Article
Uncontrolled Keywords: phosphoethanolamine lipids ; 4-hydroxy-2-nonenal ; 4-oxo-2-nonenal ; sodium permeability ; phospholipid bilayers ; molecular dynamics simulations
Subjects: NATURAL SCIENCES > Chemistry
Divisions: Division of Organic Chemistry and Biochemistry
Project titleProject leaderProject codeProject type
Molekularni aspekti oksidativnih procesa u stanicama-MolOxStressMario VazdarUIP-2014-09-6090HRZZ
Depositing User: Sofija Konjević
Date Deposited: 02 Oct 2019 09:21
Last Modified: 02 Oct 2019 09:21
DOI: 10.1016/j.freeradbiomed.2019.08.027

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