Effects of hypochlorite-modified low-density and high-density lipoproteins on intracellular Ca2+ and plasma membrane Ca(2+)-ATPase activity of human platelets.
The presence of hypochlorite-modified lipoproteins in atherosclerotic lesions suggests that HOCl, a naturally occurring oxidant formed by the myeloperoxidase-catalyzed reaction of H2O2 and Cl-, is a candidate for generation of modified lipoproteins in vivo. We have previously demonstrated that Cu(2+)-oxidized LDL inhibits platelet plasma membrane Ca(2+)-ATPase (PMCA) in isolated membranes and causes an increase in cytosolic Ca2+ in resting whole platelets. However, Cu(2+)-oxidized LDL may not be identical in structure and function to the physiologically modified lipoprotein. Since platelet function may be affected by native and modified lipoproteins, the effect of HOCl-modified LDL and HDL3 on platelet PMCA and on the free intracellular Ca2+ concentration ([Ca2+]i) of whole platelets has been investigated. We demonstrate that in contrast to Cu(2+)-oxidized LDL, HOCl-modified LDL and HDL3 stimulate platelet PMCA activity in isolated membranes and that this effect results in a decrease of [Ca2+]i in vivo. Thus, HOCl-oxidation produces modified lipoproteins with the potential for altering platelet function and with properties different from those of the Cu(2+)-oxidized counterparts.
Zabe
M
M
Department of Biochemistry, University of Louisville School of Medicine 40292, USA.
Feltzer
R E
RE
Malle
E
E
Sattler
W
W
Dean
W L
WL
D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000187:drug effects / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D016257:Fura-2 / Q000032:analysis; D006801:Humans; D006997:Hypochlorous Acid / Q000737:chemistry; D008075:Lipoproteins, HDL / Q000737:chemistry / Q000494:pharmacology*
D008075:Lipoproteins, HDL; D006997:Hypochlorous Acid; D000252:Calcium-Transporting ATPases; D002118:Calcium; D016257:Fura-2