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Publikationstyp: Zeitschriftenaufsatz
Dokumentart: Originalarbeit

Publikationsjahr: 2015

AutorInnen: Jovanovic, O; Pashkovskaya, AA; Annibal, A; Vazdar, M; Burchardt, N; Sansone, A; Gille, L; Fedorova, M; Ferreri, C; Pohl, EE

Titel: The molecular mechanism behind reactive aldehyde action on transmembrane translocations of proton and potassium ions.

Quelle: Free Radic Biol Med. 2015; 89:1067-1076



Autor/innen der Vetmeduni Vienna:

Gille Lars
Jovanovic Olga
Pashkovskaya Alina
Pohl Elena

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


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


Abstract:
Membrane transporters are involved in enormous number of physiological and pathological processes. Under oxidative stress they become targets for reactive oxygen species and its derivatives which cause protein damage and/or influence protein function(s). The molecular mechanisms of this interaction are poorly understood. Here we describe a novel lipid-mediated mechanism by which biologically important reactive aldehydes (RAs; 4-hydroxy-2-nonenal, 4-hydroxy-2-hexenal and 4-oxo-2-nonenal) modify the activity of several membrane transporters. We revealed that investigated RAs covalently modify the membrane lipid phosphatidylethanolamine (PE), that lead to the formation of different membrane active adducts. Molecular dynamic simulations suggested that anchoring of PE-RA adducts in the lipid headgroup region is primarily responsible for changes in the lipid membrane properties, such as membrane order parameter, boundary potential and membrane curvature. These caused the alteration of transport activity of mitochondrial uncoupling protein 1, potassium carrier valinomycin and ionophore CCCP. In contrast, neither direct protein modification by RAs as previously shown for cytosolic proteins, nor its insertion into membrane bilayers influenced the studied transporters. Our results explain the diversity of aldehyde action on cell proteins and open a new field in the investigation of lipid-mediated effects of biologically important RAs on membrane receptors, channels and transporters.


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