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The Hepoxilins

A Review

  • Chapter
Lipoxygenases and their Metabolites

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 447))

Abstract

This manuscript reviews the literature on hepoxilins to date. It affords a review of the structures, nomenclature, biosynthesis, catabolism and biological actions of the hepoxilins and some of their chemical analogs. Some unpublished data are also presented. The primary biological action of the hepoxilins appears to relate to their ability to release calcium from intracellular stores through a receptor-mediated action. The receptor is intracellular, and appears to be G-protein coupled. The conversion of hepoxilin into its ω-hydroxy catabolite has recently been demonstrated through the action of an ω-hydroxylase. This enzyme is different from that which oxidizes leukotriene B4, as the former activity is lost when the cell is disrupted, while leukotriene B4-catabolic activity is recovered in both the intact and disrupted cell. Additionally, hepoxilin catabolism is inhibited by CCCP, a mitochondrial uncoupler, while leukotriene catabolism is unaffected. As hepoxilins cause the translocation of calcium from intracellular stores in the endoplasmic reticulum to the mitochondria, it is speculated that hepoxilin ω-oxidation takes place in the mitochondria, and the ω-oxidation product facilitates accumulation of the elevated cytosolic calcium by the mitochondria. The biological activity of stable analogs of the hepoxilins is also described, which inhibit the calcium-releasing actions of neutrophil inflammatory mediators.

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References

  1. Pace-Asciak, C. R., Granström, E., and Samuelsson, B. (1983) J. Biol. Chem. 258, 6835–6840.

    PubMed  CAS  Google Scholar 

  2. Pace-Asciak, C. R., and Martin, J. M. (1984) Prostagl. Leukotrienes Med. 16, 173–180.

    Article  CAS  Google Scholar 

  3. Pace-Asciak, C. R. (1984) J. Biol. Chem. 259, 8332–8337.

    PubMed  CAS  Google Scholar 

  4. Pace-Asciak, C. R. (1984) Biochim. Biophys. Acta 793, 485–488.

    PubMed  CAS  Google Scholar 

  5. Pace-Asciak, C. R., Lee, S. P., and Martin, J. M. (1987) Biochem. Biophys. Res. Commun. 147, 881–884.

    Article  PubMed  CAS  Google Scholar 

  6. Bryant, R. W., and Bailey, J. M. (1980) Adv. Prostagl. Thromb. Res. 6, 95–100.

    CAS  Google Scholar 

  7. Bryant, R. W., and Bailey, J. M. (1979) Prostaglandins 17, 9–18.

    Article  PubMed  CAS  Google Scholar 

  8. Bryant, R. W., and Bailey, J. M. (1978) Fed. Proc. 37, 131.

    Google Scholar 

  9. Jones, R. L., Kerry, P. J., Poyser, N. L., Walker, I. C, and Wilson, N. H. (1978) Prostaglandins 16, 583–590.

    Article  PubMed  CAS  Google Scholar 

  10. Walker, I. C, Jones, R. L., and Wilson, N. H. (1979) Prostaglandins 18, 173–178.

    Article  PubMed  CAS  Google Scholar 

  11. Walker, L. C, Jones, R. L., Kerry, P. J., and Wilson, N. H. (1980) Adv. Prostagl. Thromb. Res. 6, 107–109.

    CAS  Google Scholar 

  12. Reynaud, D., Delton, I., Gharib, A., Sarda, N., Lagarde, M., and Pace-Asciak, C. R. (1994) J. Neurochem. 62, 126–133.

    Article  PubMed  CAS  Google Scholar 

  13. Reynaud, D., Demin, P., and Pace-Asciak, C. R. (1994) J. Biol. Chem. 269, 23976–23980.

    PubMed  CAS  Google Scholar 

  14. Pace-Asciak, C. R. (1988) Biochem. Biophys. Res. Commun. 151, 493–498.

    Article  PubMed  CAS  Google Scholar 

  15. Wolfe, L. S., and Pellerin, L. (1989) Ann. NY. Acad. Sei. (USA) 559, 74–83.

    Article  CAS  Google Scholar 

  16. Pellerin, L., and Wolfe, L. S. (1989) Soc. for Neurosci. 15, Abstract #174.14.

    Google Scholar 

  17. Feinmark, S. J., Steel, D. J., Thekkuveettil, A., Abe, M., Li, X. D., and Schwartz, J. H. (1992) Adv. Exp. Med. Biol. 318, 159–169.

    PubMed  CAS  Google Scholar 

  18. Hada, T., Hagiya, H., Suzuki, H., Arakawa, T., Nakamura, M., Matsuda, S., Yoshimoto, T., Yamamoto, S., Azekawa, T., Morita, Y., Ishimura, K., and Kim, H.-Y. (1994) Biochim. Biophys. Acta 1211, 221–228.

    PubMed  CAS  Google Scholar 

  19. Hagmann, W., Kagawa, D., Renaud, C, and Honn, K. V. (1993) Prostaglandins 46, 471–477

    Article  PubMed  CAS  Google Scholar 

  20. Hagmann, W., Gao, X., Zacharek, A., Wojciechowski, L. A., and Honn, K. V. (1995) Prostaglandins 49, 49–62.

    Article  PubMed  CAS  Google Scholar 

  21. Hansbrough, J. R., Takahashi, Y., Ueda, N., Yamamoto, S., and Holtzman, M. J. (1990) J. Biol. Chem. 265, 1771–1776.

    PubMed  CAS  Google Scholar 

  22. Izumi, T., Hoshiko, S., Rådmark, O., and Samuelsson, B. (1990) Proc. Natl. Acad. Sci. USA 87, 7477–7481.

    Article  PubMed  CAS  Google Scholar 

  23. Ishizaki, Y, and Murota, S. (1991) Neurosci. Lett. 131, 149–152.

    Article  PubMed  CAS  Google Scholar 

  24. Maruyama, T., Ueda, N., Yoshimoto, T., Yamamoto, S., Komatsu, N., and Watanabe, K. (1989) J. Histo-chem. Cytochem. 37, 1125–1131.

    Article  CAS  Google Scholar 

  25. Matsuda, S., Suzuki, H., Yoshimoto, T., Yamamoto, S., and Miyatake, A. (1991) Biochim. Biophys. Acta Lipids Lipid Metab. 1084, 202–204.

    Article  CAS  Google Scholar 

  26. Matsuda, S., Marukami, J., Yamamoto, Y, Konishi, Y, Yokoyama, C, Yoshimoto, T., Yamamoto, S., Mimura, Y, and Okuma, M. (1993) Biochim. Biophys. Acta 1180, 243–249.

    PubMed  CAS  Google Scholar 

  27. Nishiyama, M., Watanabe, T., Ueda, N., Tsukamoto, H., and Watanabe, K. (1993) J. Histochem. Cytochem. 41, 111–117.

    Article  PubMed  CAS  Google Scholar 

  28. Shinjo, F., Yoshimoto, T., Yokoyama, C, Yamamoto, S., Izumi, S.-L, Komatsu, N., and Watanabe, K. (1986) J. Biol. Chem. 261, 3377–3381.

    PubMed  CAS  Google Scholar 

  29. Sinzinger, H. (1992) Am. J. Hematol. 40, 157–158.

    Article  PubMed  CAS  Google Scholar 

  30. Takahashi, Y, Reddy, G. R., Ueda, N., Yamamoto, S., and Arase, S. (1993) J. Biol Chem. 268, 16443–16448.

    PubMed  CAS  Google Scholar 

  31. Tamai, K., Dohi, T., Ogawa, T., Okamoto, H., and Tsujimoto, A. (1990) Arch. Oral Biol. 35, 575–581.

    Article  PubMed  CAS  Google Scholar 

  32. Tomo, K., Takayama, H., Kaneko, Y, Fujita, J., Nakamura, M., Ueda, N., Yamamoto, S., and Okuma, M. (1997) Thromb. Haemost. 11, 294–297.

    Google Scholar 

  33. Watanabe, T., Medina, J. F., Haeggström, J. Z., Radmark, O., and Samuelsson, B. (1993) Eur. J. Biochem. 212, 605–612.

    Article  PubMed  CAS  Google Scholar 

  34. Yokoyama, C, Shinjo, F., Yoshimoto, T., Yamamoto, S., Izumi, S., Komatsu, N., and Watanabe, K. (1985) Hayaishi O. and S. Yamamoto (ed.). Adv. Prostagl, Thromb. Leukotriene Res., Vol. 15, Kyoto Conference on Prostaglandins, Kyoto, Japan, Raven Press, New York, pp 193–196.

    Google Scholar 

  35. Yoshimoto, T., Hagiya, H., and Yamamoto, S. (1993) In: International Symposium on Molecular Biology of the Arachidonate Cascade, Kyoto, Japan, December 5-7, 1993, Abstract pp. 55.

    Google Scholar 

  36. Hamberg, M., and Hamberg, G. (1980) Biochem. Biophys. Res. Commun. 95, 1090–1097.

    Article  PubMed  CAS  Google Scholar 

  37. Reynaud, D., and Pace-Asciak, C. R. (1997) Biochim. Biophys. Acta 1346, 305–316.

    PubMed  CAS  Google Scholar 

  38. Pace-Asciak, C. R., Klein, J., and Spielberg, S. P. (1986) Biochim. Biophys. Acta 875, 406–409.

    PubMed  CAS  Google Scholar 

  39. Pace-Asciak, C. R., and Lee, W.-S. (1989) J. Biol. Chem. 264, 9310–9313.

    PubMed  CAS  Google Scholar 

  40. Wu, W. L., and Wu, Y. L. (1993) J. Chem. Soc. Chem. Commun., 821–822.

    Google Scholar 

  41. Kato, T., Yamaguchi, Y, Ohnuma, S.-I., Uyehara, T., Namai, T., Kodama, M., and Shiobara, Y. (1986) J. Chem. Soc. Chem. Commun. 743–744.

    Google Scholar 

  42. Suemune, H., Harabe, T., and Sakai, K. (1988) Chem. Pharm. Bull. 36, 3632–3637.

    CAS  Google Scholar 

  43. Clare, A. S., Walker, G., Holland, D. L., and Crisp, D. J. (1982) Mar. Biol. Lett. 3, 113–120.

    CAS  Google Scholar 

  44. Hill, E. M., Holland, D. L., and East, J. (1993) Biochim. Biophys. Acta 1157, 297–303.

    PubMed  CAS  Google Scholar 

  45. Holland, D. L., East, J., Gibson, K. H., Clayton, E., and Oldfield, A. (1985) Prostaglandins 29, 1021–1029.

    Article  PubMed  CAS  Google Scholar 

  46. Laneuville, O., Corey, E. J., Couture, R., and Pace-Asciak, C. R. (1991) Biochim. Biophys. Acta 1084, 60–68.

    PubMed  CAS  Google Scholar 

  47. Pace-Asciak, C. R., Laneuville, O., Chang, M., Reddy, C. C, Su, W.-G., and Corey, E. J. (1989) Biochem. Biophys. Res. Commun. 163, 1230–1234.

    Article  PubMed  CAS  Google Scholar 

  48. Pace-Asciak, C. R., Laneuville, O., Su, W.-G., Corey, E. J., Gurevich, N., Wu, P., and Carlen, P. L. (1990) Proc. Natl. Acad. Sci. USA 87, 3037–3041.

    Article  PubMed  CAS  Google Scholar 

  49. Pace-Asciak, C. R., Laneuville, O., Gurevich, N., Wu, P., Carlen, P. L., Su, W.-G., Corey, E. J., Chang, M., and Reddy, C. C. (1990) In: Biological Oxidation Systems 2, Eds. C.C. Reddy, G.A. Hamilton and K.M. Kadyastha, Academic Press, New York, pp. 725–735.

    Google Scholar 

  50. Pace-Asciak, C. R., Laneuville, O., Gurevich, N., Wu, P., Carlen, P. L., and Corey, E. J. (1990) Adv. Prostagl Thromb. Leuk. Res. 21, 731–734.

    Google Scholar 

  51. Laneuville, O., Corey, E. J., Couture, R., and Pace-Asciak, C. R. (1991) Eicosanoids 4, 95–97.

    PubMed  CAS  Google Scholar 

  52. Reynaud, D., Rounova, O., Demin, P. M., Pivnitzky, K. K., and Pace-Asciak, C. R. (1997) Biochim. Biophys. Acta 1348, 287–298.

    PubMed  CAS  Google Scholar 

  53. Pace-Asciak, C. R., Martin, J. M., Corey, E. J., and Su, W.-G. (1985) Biochem. Biophys. Res. Commun. 128, 942–946.

    Article  PubMed  CAS  Google Scholar 

  54. Pace-Asciak, C. R., Martin, J. M., and Corey, E. J. (1986) Prog. Lipid Res. 25, 625–628

    Article  PubMed  CAS  Google Scholar 

  55. Nathan, M. H., and Pek, S. B. (1989) Diabetes Suppl 2, Abstract #784.

    Google Scholar 

  56. Derewlany, L. O., Pace-Asciak, C. R., and Radde, I. C. (1984) Can. J. Physiol Pharmacol. 62, 1466–1469.

    Article  PubMed  CAS  Google Scholar 

  57. Laneuville, O., Couture, R., and Pace-Asciak, C. R. (1992) Br. J. Pharmacol. 105, 297–304.

    PubMed  CAS  Google Scholar 

  58. Dho, S., Grinstein, S., Corey, E. J., Su, W. G., and Pace-Asciak, C. R. (1990) Biochem. J. 266, 63–68.

    PubMed  CAS  Google Scholar 

  59. Laneuville, O., Reynaud, D., Grinstein, S., Nigam, S., and Pace-Asciak, C. R. (1993) Biochem. J. 295, 393–397.

    PubMed  CAS  Google Scholar 

  60. Mills, L., Reynaud, D., and Pace-Asciak, C. R. (1997) Exp. Cell Res. 230, 337–341.

    Article  PubMed  CAS  Google Scholar 

  61. Margalit, A., Sofer, Y., Grossman, S., Reynaud, D., Pace-Asciak, C. R., and Livne, A. (1993) Proc. Natl. Acad. Sci. USA 90, 2589–2592.

    Article  PubMed  CAS  Google Scholar 

  62. Carlen, P. L., Gurevich, N., Wu, P. H., Su, W.-G., Corey, E. J., and Pace-Asciak, C. R. (1989) Brain Res. 497, 171–176.

    Article  PubMed  CAS  Google Scholar 

  63. Carlen, P. L., Gurevich, N., Zhang, L., Wu, P. H., Reynaud, D., and Pace-Asciak, C. R. (1994) Neuroscience 58, 493–502.

    Article  PubMed  CAS  Google Scholar 

  64. Piomelli, D. A., Volterra, A., Dale, R, Siegelbaum, S. A., Kandel, E., Schwartz, J. H., and Belardetti, F. (1987) Nature 328, 38–43.

    Article  PubMed  CAS  Google Scholar 

  65. Belardetti, F., Campbell, W. B., Falck, J. R., Demontis, G., and Rosolowsky, M. (1989) Neuron 3, 497–505.

    Article  PubMed  CAS  Google Scholar 

  66. Belardetti, F., and Siegelbaum, S. A. (1988) TINS 11, 232–238.

    PubMed  CAS  Google Scholar 

  67. Feinmark, S. J., Piomelli, D., Shapiro, E., and Schwartz, J. H. (1989) Ann. NY Acad. Sci. 559, 121–130.

    Article  PubMed  CAS  Google Scholar 

  68. Piomelli, D., Shapiro, E., Zipkin, R., Schwartz, J. H., and Feinmark, S. J. (1989) Proc. Natl. Acad. Sci. USA 86, 1721–1725.

    Article  PubMed  CAS  Google Scholar 

  69. Lin, Z., Laneuville, O., and Pace-Asciak, C. R. (1991) Biochem. Biophys. Res. Commun. 179, 52–56.

    Article  PubMed  CAS  Google Scholar 

  70. Laneuville, O., Couture, R., and Pace-Asciak, C. R. (1992) Br. J. Pharmacol. 107, 808–812.

    PubMed  CAS  Google Scholar 

  71. Laneuville, O., Corey, E. J., Couture, R., and Pace, A. C. R. (1991) Biochim. Biophys. Acta Lipids Lipid. Metab. 1084, 60–68.

    Article  CAS  Google Scholar 

  72. Laneuville, O., Corey, E. J., and Pace-Asciak, C. R. (1991) In: Prostaglandins, Leukotrienes, Lipoxins & PAF, XIth, Washington International Spring Symposium, Ed. Martyn Bailey, Plenum Press, New York, 1991, pp. 335–338.Abstract # 155.

    Google Scholar 

  73. Reynaud, D., Demin, P. M., and Pace-Asciak, C. R. (1995) Biochem. Biophys. Res. Commun. 207, 191–194.

    Article  PubMed  CAS  Google Scholar 

  74. Reynaud, D., Demin, P., and Pace-Asciak, C. R. (1996) Biochem. J. 313, 537–541.

    PubMed  CAS  Google Scholar 

  75. Demin, P. M., Kochev, D. M., Perrier, H., Pace-Asciak, C. R., and Pivnitsky, K. K. (1997) Mendeleev. Commun. 1–2.

    Google Scholar 

  76. Jaconi, M. E. E., Lew, D. P., Monod, A., and K-H., K. (1993) J. Biol. Chem. 268, 26075–26078.

    PubMed  CAS  Google Scholar 

  77. Demin, P. M., and Pace-Asciak, C. R. (1993) Tetrahedron Lett. 34, 4305–4308.

    Article  CAS  Google Scholar 

  78. Demin, P., Reynaud, D., and Pace-Asciak, C. R. (1996) J. Lipid Med. Cell Signalling 13, 63–72.

    Article  CAS  Google Scholar 

  79. Nigam, S., Nodes, S., Cichon, G., Corey, E. J. and Pace-Asciak, C. R. (1990) Biochem. Biophys. Res. Commun. 171, 944–948.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine University of Toronto, Canada, M5S 1A8

    Cecil R. Pace-Asciak (Prof.)

  2. Research Institute, Hospital for Sick Children 555 University Avenue, Toronto, Canada, M5G 1X8

    Denis Reynaud & Peter Demin

  3. Department of Gynecology, University Medical Center Benjamin Franklin Free University of Berlin, D-12200, Berlin, Germany

    Cecil R. Pace-Asciak (Prof.) & Santosh Nigam

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  1. Cecil R. Pace-Asciak
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  2. Denis Reynaud
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  1. Free University of Berlin, Berlin, Germany

    Santosh Nigam

  2. Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada

    Cecil R. Pace-Asciak

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© 1999 Kluwer Academic/Plenum Publishers, New York

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Pace-Asciak, C.R., Reynaud, D., Demin, P., Nigam, S. (1999). The Hepoxilins. In: Nigam, S., Pace-Asciak, C.R. (eds) Lipoxygenases and their Metabolites. Advances in Experimental Medicine and Biology, vol 447. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4861-4_12

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  • DOI: https://doi.org/10.1007/978-1-4615-4861-4_12

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