Platelet-aggregating effects of platelet-activating factor-like phospholipids formed by oxidation of phosphatidylcholines containing an sn-2-polyunsaturated fatty acyl group.
Previously, we reported the formation of four kinds of phosphatidylcholines (PC) with a short-chain monocarboxylate, dicarboxylate, dicarboxylate semialdehyde or omega-hydroxymonocarboxylate group by oxidation of PCs containing polyunsaturated fatty acid (PUFA) in an FeSO4/ascorbate/EDTA system. In this study, we identified these novel phospholipids by GC-MS as oxidation products of two alkyl ether-linked PCs, 1-O-hexadecyl-2-docosahexaenoyl and 1-O-hexadecyl-2-arachidonoyl-sn-glycero-3- phosphocholine (GPC). The sn-2-acyl moieties of oxidatively fragmented PCs derived from PCs containing docosahexaenoate were one methylene unit shorter than those detected as major oxidation products of PCs containing arachidonate. The platelet-aggregations induced by the oxidized PCs were all inhibited by FR-900452, an antagonist of platelet activating factor (PAF). The PAF-like activity of oxidized 1-O-hexadecyl-2-docosahexaenoyl-GPC, which was equivalent of 1372 +/- 262 pmol 16:0-PAF/mumol starting PC, was 5 times that of oxidized 1-O-hexadecyl-2-arachidonoyl-GPC and 150 times that of oxidized 1-palmitoyl-2-docosahexaenoyl-GPC, suggesting that both an sn-1-alkyl ether linkage and an sn-2-acyl group with a short chain length are important structural requirements for induction of platelet aggregation. These possibilities were confirmed by experiments on the platelet-aggregating activities of synthetic PAF-like compounds. Quantitative measurements by GC-MS of PAF-like phospholipids formed by lipid peroxidation and the activities of synthetic PAF-like phospholipids, suggested that the activities of most oxidized PCs containing PUFA were ascribable to those of PCs with an sn-2-short-chain monocarboxylate group.
Tanaka
T
T
Faculty of Pharmaceutical Sciences, University of Tokushima, Japan.
Iimori
M
M
Tsukatani
H
H
Tokumura
A
A
D000818:Animals; D005231:Fatty Acids, Unsaturated / Q000032:analysis*; D008401:Gas Chromatography-Mass Spectrometry; D008297:Male; D010084:Oxidation-Reduction; D010713:Phosphatidylcholines / Q000737:chemistry* / Q000378:metabolism; D010743:Phospholipids / Q000138:chemical synthesis; D010972:Platelet Activating Factor / Q000138:chemical synthesis*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis*; D011817:Rabbits
D005231:Fatty Acids, Unsaturated; D010713:Phosphatidylcholines; D010743:Phospholipids; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors