title: Behavior of 4-hydroxynonenal in phospholipid membranes.
abstract: Under conditions of oxidative stress, 4-hydroxy-2-nonenal (4-HNE) is commonly present in vivo. This highly reactive and cytotoxic compound is generated by oxidation of lipids in membranes and can be easily transferred from a membrane to both cytosol and the extracellular space. Employing time-dependent fluorescence shift (TDFS) method and molecular dynamics simulations, we found that 4-HNE is stabilized in the carbonyl region of a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayer. 4-HNE is thus able to react with cell membrane proteins and lipids. Stabilization in the membrane is, however, moderate and a transfer of 4-HNE to either extra- or intracellular space occurs on a microsecond time scale. These molecular-level details of 4-HNE behavior in the lipid membrane rationalize the experimentally observed reactivity of 4-HNE with proteins inside and outside the cell. Furthermore, these results support the view that 4-HNE may play an active role in cell signaling pathways.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic and Center for Biomolecules and Complex Molecular Systems, 16610 Prague 6, Czech Republic.
authors.forename: Mario
authors.initials: M
authors.lastname: Vazdar
authors.forename: Piotr
authors.initials: P
authors.lastname: Jurkiewicz
authors.forename: Martin
authors.initials: M
authors.lastname: Hof
authors.forename: Pavel
authors.initials: P
authors.lastname: Jungwirth
authors.forename: Lukasz
authors.initials: L
authors.lastname: Cwiklik
mesh_terms: D000447:Aldehydes / Q000737:chemistry*; D005453:Fluorescence; D008051:Lipid Bilayers / Q000737:chemistry*; D008567:Membranes, Artificial; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D010713:Phosphatidylcholines / Q000737:chemistry*
chemical_list: D000447:Aldehydes; D008051:Lipid Bilayers; D008567:Membranes, Artificial; D010713:Phosphatidylcholines; C027576:4-hydroxy-2-nonenal; C028694:1-palmitoyl-2-oleoylphosphatidylcholine