Transformation of 15-Hydroperoxyeicosapentaenoic Acid Into Mono-and Dihydroxyeicosapentaenoic Acids by Human Platelets
[1-14C]-15-hydroperoxyeicosapentaenoic acid was incubated with suspensions of washed human platelets. Two dihydroxy and one monohydroxy metabolites were isolated and purified by RP-HPLC and SPHPLC. GC/MS analysis revealed that the three metabolites were: 8,15-dihydroxyeicosapentaenoic acid, 14,15-dihydroxyeicosapentaenoic acid and 15-hydroxyeicosapentaenoic acid. In addition, the non-enzymatic generation of an allylic hydroxy-epoxide metabolite (13-hydroxy-14,15-epoxyeicosapentaenoic acid) was identified. Furthermore, 15-HEPE was demonstrated to be a potent inhibitor of fMLP-induced neutrophil aggregation. Thus, transformation of the 15-lipoxygenase product of eicosapentaenoic acid by platelets may generate biologically active compounds that modulate neutrophil function.
KeywordsHPLC Hexane Diethyl Proteinuria Indomethacin
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- 5.T. W. Weiner and H. Sprecher, Arachidonic acid 5,8,11-eicosatetrienoic acid and 5,8,11,14,17-eicosapentaenoic acid. Dietary manipulation of the levels of these acids in rat liver and platelet phospholipids and their incorporation into human platelet lipids, Biochim. Biophys. Acta 792: 293 (1984).Google Scholar
- 6.S. Hammarstrom, Biochim. Biophys. Acta 663: 575 (1981).Google Scholar
- 9.S. M. Prescott, The effect of eicosapentaenoic acid on leukotriene B production by human neutrophils, J. Biol. Chem., 242: 5329 (1967).Google Scholar
- 11.G. Graff, Preparation of 15-L-hydroperoxy-5,8,11,13-eicosatetraenoic acid (15-HPETE), in: “Methods in Enzymology,” W. E. M. Lands and W. L. Smith, eds., Academic Press, New York (1982).Google Scholar
- 13.F. F. Sun and J. C. McGuire, Characterization of the enzymatic reactions that lead to the synthesis of leukotriene B4, Biochim. Biophys. Acta 794: 56 (1984).Google Scholar
- 16.S. Marumiya, J. S. Salmon, F. H. Cottee, B. C. Weatherley and R. J. Flower, Arachidonic acid 15-lipoxygenase from rabbit peritoneal polymorphonuclear leukocytes. Partial purification and properties, J. Biol. Chem. 256: 9583 (1981).Google Scholar
- 17.G. Eglington, D. H. Hunneman and A. McCormick, in: “Organic Mass Spectrometry,” Academic Press, New York (1968).Google Scholar
- 19.P. Y-K Wong, R. A. Hughes and B. Lam, Lipoxene: A new group of trihydroxy pentaene of eicosapentaenoic acid derived from porcine leukocytes, Biochem. Biophys. Res. Commun., submitted (1984).Google Scholar
- 23.P. Y-K Wong, P. Westlund, E. Granstrom, M. Hamberg, P. H-W Chao and B. Samuelsson, Effects of bradykinin (BK) on the metabolism of arachidonic acid (AA) in human platelets and polymorphonuclear leukocytes: Formation of 15-lipoxygenase products, Thromb. Haemostas. 50: 389 (1983).Google Scholar