Transformation of 15-Hydroperoxyeicosapentaenoic Acid Into Mono-and Dihydroxyeicosapentaenoic Acids by Human Platelets

  • Bing Lam
  • Ewa Marcinkiewicz
  • Patrick Y-K Wong
Part of the NATO ASI Series book series (NSSA, volume 95)

Summary

[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.

Keywords

HPLC Hexane Diethyl Proteinuria Indomethacin 

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References

  1. 1.
    P. Needleman, A. Raz, M. S. Minkes, J. A. Ferrendelli, H. Sprecher, Triene prostaglandins: prostacyclin and thromboxane biosynthesis and unique biological properties, Proc. Natl. Acad. Sci. 76: 944 (1979).PubMedCrossRefGoogle Scholar
  2. 2.
    M. O. Whitaker, A. Wyche, F. Fitzpatrick, H. Sprecher and P. Needleman, Triene prostaglandins: prostaglandin D3 and eicosapentaenoic acid as potential antithrombotic substances, Proc. Natl. Acad. Sci. 76: 5919 (1979).PubMedCrossRefGoogle Scholar
  3. 3.
    K. Ochi, T. Yoshimoto, S. Yamamoto, K. Taniguchi and T. Miyamoto, Arachidonate 5-lipoxygenase of guinea-pig peritoneal polymorphonuclear leukocytes. Activation by adenosine, J. Biol. Chem. 258: 5754 (1983).PubMedGoogle Scholar
  4. 4.
    R. C. Murphy, W. C. Pickett, B. R. Culp and W. E. M. Lands, Tetraene and pentaene leukotrienes: selective production from murine mastocytoma cells after dietary manipulation, Prostaglandins 22: 613 (1981).PubMedCrossRefGoogle Scholar
  5. 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. 6.
    S. Hammarstrom, Biochim. Biophys. Acta 663: 575 (1981).Google Scholar
  7. 7.
    L. Orning, R. Bernstrom and S. Hammarstrom, Formation of leukotrienes E3, E4 and E5 in rat basophilic leukemia cells, Eur. J. Biochem. 120: 41 (1981).PubMedCrossRefGoogle Scholar
  8. 8.
    A. G. Leitch, T. H. Lee, E. W. Ringel, J. D. Prickett, D. R. Robinson, E. J. Corey, J. M. Drazen, K. F. Austen and R. A. Lewis, Immunologically induced generation of tetraene and pentaene leukotrienes in peritoneal cavities of menhaden-fed rats, J. Immunol. 132: 2559 (1984).PubMedGoogle Scholar
  9. 9.
    S. M. Prescott, The effect of eicosapentaenoic acid on leukotriene B production by human neutrophils, J. Biol. Chem., 242: 5329 (1967).Google Scholar
  10. 10.
    M. Hamberg and B. Samuelsson, On the specificity of the oxygenation of unsaturated fatty acids catalyzed by soybean lipoxidase, J. Biol. Chem. 242: 5329 (1967).PubMedGoogle Scholar
  11. 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
  12. 12.
    M. Hamberg and B. Samuelsson, Prostaglandin endoperoxides. Novel transformations of arachidonic acid in human platelets, Proc. Natl. Acad. Sci. 71: 3400 (1974).PubMedCrossRefGoogle Scholar
  13. 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
  14. 14.
    P. Y-K Wong, P. Westlund, M. Hamberg, E. Granstrom, P. H-W Chao and B. Samuelsson, ω-Hydroxylation of 12-L-hydroxy5,8,10,14-eicosatetraenoic acid in human polymorphonuclear leukocytes, J. Biol. Chem. 259: 2683 (1984).PubMedGoogle Scholar
  15. 15.
    R. W. Bryant and J. M. Bailey, Rearrangement of 15-hydroperoxyeicosatetraenoic acid (15-HPETE) during incubations with hemoglobin: a model for platelet lipoxygenase metabolism, Proc. Lipid Res. 20: 279 (1981).CrossRefGoogle Scholar
  16. 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. 17.
    G. Eglington, D. H. Hunneman and A. McCormick, in: “Organic Mass Spectrometry,” Academic Press, New York (1968).Google Scholar
  18. 18.
    W. Jubiz, O. Radmark, J. K. Lindgren, C. Malmsten and B. Samuelsson, Novel leukotrienes: products formed by initial oxygenation of arachidonic acid at C-15, Biochem. Biophys. Res. Commun. 99: 976 (1981).CrossRefGoogle Scholar
  19. 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
  20. 20.
    J. Y. Vanderhoek, R. W. Bryant and J. M. Bailey, Inhibition of leukotriene biosynthesis by the leukocyte product 15-hydroxy-5,8,11,13-eicosatetraenoic acid, J. Biol. Chem. 255: 10064 (1980).PubMedGoogle Scholar
  21. 21.
    J. Y. Vanderhoek, R. W. Bryant and J. M. Bailey, 15-hydroxy5,8,11,13-eicosatetraenoic acid: a potent and selective inhibitor of platelet lipoxygenase, J. Biol. Chem. 255: 5996 (1980).PubMedGoogle Scholar
  22. 22.
    J. M. Bailey, R. W. Bryant, C. E. Low, M. B. Pupillo and J. Y. Vanderhoek, Regulation of T-lymphocyte mitogenesis by the leukocyte product 15-hydroxy-eicosatetraenoic acid (15-HETE), J. Cell. Immunol. 67: 112 (1982).CrossRefGoogle Scholar
  23. 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
  24. 24.
    J. Dyerberg, H. O. Bang, E. Stofferson, S. Moncada and J. R. Vane, Eicosapentaenoic acid and prevention of thrombosis and atherosclerosis, Lancet 2: 117 (1978).PubMedCrossRefGoogle Scholar
  25. 25.
    J. D. Prickett, D. R. Robinson and A. D. Steinberg, Dietary enrichment with the polyunsaturated fatty acid eicosapentaenoic acid prevents proteinuria and prolongs survival in NZBXNZW Fl mice, J. Clin. Invest. 68: 556 (1981).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • Bing Lam
    • 1
  • Ewa Marcinkiewicz
    • 1
  • Patrick Y-K Wong
    • 1
  1. 1.Department of PharmacologyNew York Medical CollegeValhallaUSA

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