Effects of 4-OH-2,3-trans-nonenal on human erythrocyte plasma membrane Ca2+ pump and passive Ca2+ permeability

Structural and functional alterations of cell membranes caused by free radicals leading to lipid peroxidation and increases in intracellular Ca2+ concentrations have been implicated in atherogenesis. The objective of this study was to directly measure the effects of a major aldehydic lipid peroxidation product, 4-OH-nonenal (HNE), on plasma membrane Ca2+ regulatory mechanisms. This was attained by measuring passive Ca2+ permeability, primary active Ca2+-transport, and (Ca2+ + Mg2+)-ATPase activity in a human red cell model system. Using this three-pronged approach it could be shown that HNE increases passive Ca2+ permeability significantly beyond the typically low basal flux, while at the same time inhibiting the active Ca2+ extrusion pump and associated (Ca2+ + Mg2+)-ATPase activity. We conclude that this deleterious combination of effects by HNE in this plasma membrane model system may be indicative of plasma membrane changes in cells directly involved in atheroma formation and thus may represent causative factors in the early stages of atherogenesis.