Naslov
The molecular mechanism behind reactive aldehyde action on transmembrane translocations of proton and potassium ions

Autori
Jovanović, Olga ; Pashkovskaya, Alina, A. ; Annibal, Andrea ; Vazdar, Mario ; Burchardt, Nadine ; Sansone, Anna ; Gille, Lars ; Fedorova, Maria ; Ferreri, Carla ; Pohl, Elena E.

Izvornik
Free radical biology & medicine (0891-5849) 89 (2015); 1067-1076

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
reactive aldehydes ; oxidative stress ; phospholipid adducts ; proton conductance

Sažetak
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 RA as previously shown for cytosolic proteins, nor RAs 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 RA on membrane receptors, channels and transporters.

Izvorni jezik
Engleski

Znanstvena područja
Fizika, Kemija, Biologija

POVEZANOST RADA