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, Mg(2+)-ATPase, Ca(2+)-ATPase, and calmodulin-stimulated Ca(2+)-ATPase has been studied both in erythrocyte ghosts and in neutrophil membrane preparations. Neutrophil Ca(2+)-ATPase was strongly inhibited by micromolar concentrations of HNE (IC(50) = 12 microM), that means in the range of pathophysiologically relevant HNE levels. The IC(50) value for neutrophil Na(+)/K(+)-ATPase was about 40 microM. HNE was considerably less effective against neutrophil Mg(2+)-ATPase and the erythrocyte ghost enzymes (IC(50) values range from 91 to 240 microM). The data suggest that HNE may play a specific role in the regulation of neutrophil calcium homeostasis in response to oxidative stress.
Siems
W
W
Herzog-Julius Hospital for Rheumatology and Orthopaedics, D-38667 Bad Harzburg, Germany.
Capuozzo
E
E
Lucano
A
A
Salerno
C
C
Crifò
C
C
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000447:Aldehydes / Q000494:pharmacology*; D001693:Biological Transport, Active / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D004229:Dithiothreitol / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000201:enzymology; D006801:Humans; D019811:Hydroxylamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology*; D013439:Sulfhydryl Reagents / Q000494:pharmacology
D000447:Aldehydes; D007527:Isoenzymes; D013439:Sulfhydryl Reagents; D019811:Hydroxylamine; D000251:Adenosine Triphosphatases; C027576:4-hydroxy-2-nonenal; D004229:Dithiothreitol