Effect of Reactive Aldehydes on Ionophore-Mediated Transmembrane Translocations of H+ and K+

Abstract

Reactive aldehydes (RA) are involved in the onset and progression of many pathologies such as cardiovascular and neurodegenerative diseases. The precise mechanisms by which aldehydes contribute to these diseases remain unclear. Previously, we and other groups suggested that RAs modify the membrane protein function by either binding to the proteins directly(1) or to aminophosphosholipids, with a subsequent alteration in protein conformation. Here, we investigated the influence of biologically important RAs such as 4-hydroxy-2-nonenal (HNE), 4-oxo-2-nonenal (ONE) and 4-hydroxy-2-hexenal (HHE) on the transport kinetics of the ionophores carbonyl-cyanide-m-chlorophenylhydrazone (CCCP) and valinomycin (Val). We found that RA increases the membrane conductance, G, in the presence of Val in the following order ONE>HNE>HHE. In contrast G decreases in the presence of CCCP and ONE. The presence of phosphatidylethanolamine in the membrane was crucial for the effect to occur. The results are consistent with the hypothesis that RA adducts alter membrane boundary potential.1. E. A. Malingriaux, et al., “Fatty Acids are Key in 4-Hydroxy-2-Nonenal-Mediated Activation of Uncoupling Proteins 1 and 2” PLoS. ONE. 8(10), e77786 (2013).