Formation and Role of Lipoxygenase Products in Human Platelets
Blood platelets are involved in primary hemostasis through their aggregation in response to different agents. When platelets are aggregated by some of these agents such as thrombin or collagen, polyunsaturated fatty acids (mainly arachidonic acid) are liberated from membrane phospholipids and then subsequently oxygenated via cyclooxygenase and/or lipoxygenase. The cyclooxygenase pathway has been well documented (Smith, 1980). From arachidonic acid (AA), it leads to proaggregatory prostanoids, prostaglandin endoperoxides (PGG2/PGH2) and thromboxane A2 (TxA2), which together with 12-hydroxyheptadecatrienoic acid represent the main compounds of the pathway, primary prostaglandins being minor products. In comparison, dihomo-γ-linolenic acid (DHLA) and 5,8,11,14,17-eicosapentaenoic acid (EPA), precursors of mono- and trienoic series prostanoids, respectively, are well known to be inhibitors of platelet functions (Willis, 1981). Less data about platelet lipoxygenase pathway, especially for its biological role, are available. This enzyme is assumed to be a 12-lipoxygenase (Hamberg et ai., 1974; Nugteren, 1975) associated with a glutathione-dependent peroxidase (Bryant and Bailey, 1980). It has been reported that 12-hydroperoxyeicosatetraenoic acid (12-HPETE), the lipoxygenase product of AA, is able to inhibit both thromboxane synthase (Hammarström and Falardeau, 1977) and platelet diglyceride lipase (Rittenhouse-Simmons, 1980). More recently, 12-HPETE was described as an inhibitor of PGH2/TxA2-induced platelet aggregation (Aharony et al., 1982).
KeywordsArachidonic Acid Platelet Aggregation Human Platelet Lipoxygenase Activity Lipoxygenase Pathway
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- Lagarde, M., Authi, K.S., and Crawford, N., 1982, Fatty acid specificity of human platelet-membrane phospholipase A2 and diacylglycerol lipase, Biochem. Soc. Trans. 10:241–243.Google Scholar
- MacKean, M.L., Smith, J.B., and Silver, M.J., 1981, Formation of lysophosphatidylcholine by human platelets in response to thrombin, J. Biol. Chem. 256:1522–1524.Google Scholar
- Marcus, A.J., Broeckman, M.J., Saner, L.B., Ullman, H.L., Islam, N., Serham, C.N., Rutherford, L.E., Korchak, H.M., and Weissmann, G., 1982, Formation of leukoktrienes and other hydroxy acids during platelet-neutrophil interactions in vivo, Biochem. Biophys. Res. Commun. 109:130–137.PubMedCrossRefGoogle Scholar
- Rittenhouse-Simmons, S., 1980, Indomethacin-induced accumulation of diglyceride in activated human platelets, J. Biol. Chem. 225:2259–2262.Google Scholar
- Smith, J.B., 1980, The prostanoids in hemostasis and thrombosis, Am. J. Pathol 99:742–804.Google Scholar