Lipid peroxide overcomes the inability of platelet secretory phospholipase A2 to hydrolyze membrane phospholipids in rabbit platelets.
The present study investigated the effect of lipid peroxide on the ability of group IIA secretory phospholipase A2 (IIAsPLA2) to hydrolyze platelet membrane phospholipids. The treatment of rabbit platelets with tert-butyl hydroperoxide (BHP) and FeSO4 generated malondialdehyde, an index of lipid peroxidation, and slightly induced arachidonic acid liberation and lysophosphatidylcholine formation. Further addition of IIAsPLA2 purified from rabbit platelets synergistically enhanced the liberation and the formation induced by the oxidizing reagents, although the enzyme alone did not. When the IIAsPLA2 was pretreated with heparin, the enhancement was not observed. The combination of IIAsPLA2 with linoleic acid hydroperoxide and FeSO4 also caused synergistic arachidonic acid liberation. Furthermore, IIAsPLA2 enhanced thromboxane B2 generation and platelet aggregation induced by BHP and FeSO4. The synergistic aggregation was sensitive to indomethacin. With a membrane fraction as a substrate, IIAsPLA2 caused arachidonic acid liberation, which was enhanced in the presence of BHP and FeSO4. These results suggest that modification of membrane phospholipids by oxidizing reagents increases the accessibility of the membrane to platelet IIAsPLA2, and sequential enhancement of arachidonic acid liberation may contribute to the propagation of oxidative stress-induced cellular injury.
Akiba
S
S
Department of Pathological Biochemistry, Kyoto Pharmaceutical University, Misasagi.
Nagatomo
R
R
Hayama
M
M
Sato
T
T
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D006868:Hydrolysis; D007249:Inflammation; D008054:Lipid Peroxides / Q000494:pharmacology*; D008563:Membrane Lipids / Q000378:metabolism*; D018384:Oxidative Stress; D010741:Phospholipases A / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism*; D011817:Rabbits
D008054:Lipid Peroxides; D008563:Membrane Lipids; D010743:Phospholipids; D010741:Phospholipases A; D054467:Phospholipases A2