High sensitivity of plasma membrane ion transport ATPases from human neutrophils towards 4-hydroxy-2,3-trans-nonenal

Lipid peroxidation results in release of 4-hydroxy-2,3-trans-nonenal (HNE), which is known to conjugate to specific amino acids of proteins and may alter their function. The effect of HNE on the activities of Na+/K(+)ATPase, Mg2+-ATPase, Ca2+-ATPase, and calmodulin-stimulated Ca2+-ATPase has been studied both in erythrocyte ghosts and in neutrophil membrane preparations. Neutrophil Ca2+-ATPase was strongly inhibited by micromolar concentrations of HNE (IC50 = 12 muM), that means in the range of pathophysiologically relevant HNE levels. The IC50 value for neutrophil Na+/K+-ATPase was about 40 muM. HNE was considerably less effective against neutrophil Mg2+-ATPase and the erythrocyte ghost enzymes (IC50 values range from 91 to 240 muM). The data suggest that HNE may play a specific role in the regulation of neutrophil calcium homeostasis in response to oxidative stress. (C) 2003 Elsevier Inc. All rights reserved.