Advertisement

Xanthine Oxidase is not Likely to be a Source of Injurious Free Radicals in the Ischemic Human Heart: A Study of Species Differences

  • James M. Downey
  • Lynne J. Eddy
  • Chiaki Shirato
  • Patricia Molina
  • Miguel Molina
Chapter
  • 48 Downloads
Part of the Developments in Cardiovascular Medicine book series (DICM, volume 86)

Abstract

Oxygen derived free radicals appear to contribute to ischemia-reperfusion injury in the heart (1,2). The source of these radicals, however, remains a subject of current debate. Studies from this laboratory indicate that xanthine oxidase is an important source of cytotoxic free radicals in the reperfused dog heart (3). Xanthine oxidase can produce oxi-radicals by the following mechanism. During ischemia ATP in the myocyte is degraded through several intermediates to hypoxanthine (4) which is the substrate for cardiac xanthine oxidase. This enzyme, which is thought to reside exclusively in the coronary capillary endothelium (5), oxidizes hypoxanthine to urate. An important feature of the xanthine oxidase hypothesis is the conversion of xanthine dehydrogenase to xanthine oxidase. The enzyme is thought to exist primarily as a dehydrogenase in normal myocardium and in this state it can only use NAD+ as the electron acceptor during the oxidation of purines (6,7). Thirty minutes of ischemia in the dog heart caused about 30% of the enzyme to be converted to the oxidase form (3) which can utilize molecular oxygen as an electron acceptor, reducing that oxygen to Superoxide and hydrogen peroxide (8).

Keywords

Infarct Size Xanthine Oxidase Rabbit Heart Xanthine Oxidase Activity Xanthine Dehydrogenase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    McCord, J.M. New England J. Med. 312:159–163, 1985.CrossRefGoogle Scholar
  2. 2.
    Hess, M.L. and Manson, N. J. Mol. Cell Cardiol. 16:969 – 985, 1984.PubMedCrossRefGoogle Scholar
  3. 3.
    Chambers, D.E., Parks, D.A., Patterson, G., Roy, R., McCord J.M., Yoshida, S., Parmley, L.F. and Downey, J.M. J. Mol. Cell. Cardiol. 17:145–152, 1985.PubMedCrossRefGoogle Scholar
  4. 4.
    Jennings, R.B., Reimer, K.A. Circ Res 49, 892–899, 1981.PubMedCrossRefGoogle Scholar
  5. 5.
    Jarasch, E.D., Bruder, G., Heid, H.W. Acta. Physiol. Scand. Suppl. 548:39–46, 1986.PubMedGoogle Scholar
  6. 6.
    Batelli, M.G., Lorenzoni, E., Stripe, F. Biochem. J. 131, 191–198, 1973.Google Scholar
  7. 7.
    Roy, R.S., McCord, J.M. in: Proceedings of the Third International Conference on Superoxide and Superoxide Dismutase (ed. R. Greenwald and G. Cohen), Elsevier/North Holland Biomedical Press, New York, pp 145–153, 1983.Google Scholar
  8. 8.
    Fridovich, I. J. Biol. Chem. 245:4053–4057, 1970.PubMedGoogle Scholar
  9. 9.
    Werns, S.W., Shea, M.J., Mitsos, S.E., Dysko, R.C., Fantone J.C., Schork, M.A., Abrams, G.D., Pitt, B., and Lucchesi, B.R. Circulation 73:518–524, 1986.PubMedCrossRefGoogle Scholar
  10. 10.
    Manning, A.S., Coltart D.J. and Hearse, D.J. Circ. Res. 55: 545–548, 1984PubMedCrossRefGoogle Scholar
  11. 11.
    Bednar, M., Smith, B., Pinto, A., Mullane, K. Circ. Res. 57: 131–141, 1985PubMedCrossRefGoogle Scholar
  12. 12.
    Markley, H.G., Faillace, L.A. and Mezey, E. Biochem. Biophysics Acta. 309:23–31, 1973Google Scholar
  13. 13.
    Reimer, K.A., Jennings, R.B. Lab. Invest. 40:633–644, 1979.PubMedGoogle Scholar
  14. 14.
    Ketai, L., Grum, C., Meyers, C., Shlafer, M. Circulation 72: III-357, 1985.Google Scholar
  15. 15.
    Romson, J., Hook, B., Abrams, G., Schork, A., Luchessi, B.R. Circulation 67:1016–1023, 1983,PubMedCrossRefGoogle Scholar
  16. 16.
    Meyers, C.L., Weiss, S.J., Kirsh, M.M., Shlafer, M. J. Mol. Cell. Cardiol. 17:673–684, 1985.Google Scholar
  17. 17.
    Bhimji, S., Godin, D.V., McNeill, J.H. Fed Proc 44:1480, 1985.Google Scholar
  18. 18.
    Grum, C.M., Ketai, L.H., Myers, C.L. and Shlafer M. Am. J. Physiol. 252:H368-H373, 1987.PubMedGoogle Scholar
  19. 19.
    Toyo-oka, T., Kamishiro, T., Fumino, H., Masaki, T., Hosoda, S. Japanese Heart J. 25:623–632, 1984.CrossRefGoogle Scholar
  20. 20.
    Schaper, W. in: Thereputic approaches to Myocardial Infarct Size Limitation, ed. D.J. Hearse and D.M. Yellon. Raven Press, New York, 1984.Google Scholar
  21. 21.
    Krenitsky, T.A., Tuttle, J.V. Cattau, E.L., Wang P.A. Comp. Biochem. Physiol. 49:687–703, 1974.Google Scholar
  22. 22.
    Watts, R.W.E., Watts J.E.M., Seegmiller, J.E. J. Lab. Clin. Med. 66:688–697, 1965.PubMedGoogle Scholar
  23. 23.
    Kherer, J.P. Piper, H.M., Sies, H. Free Radical Com. 3:69–78, 1987CrossRefGoogle Scholar
  24. 24.
    Parks, D.A. and Granger D.N. Acta. Physiol. Scand. 126(supp 584):87–100, 1986.Google Scholar
  25. 25.
    Clare, D.A., Blakitone, B.A., Swasigood, H.E., Horton, H.R. Acta. Biochem. Biophysics 211:44–47, 1973.Google Scholar
  26. 26.
    Stripe, F., Delia Corte, E. Acta. Biochem. Biophys. 212:195–197, 1970.Google Scholar
  27. 27.
    Parks, D.A., Bulkley, G.B., Granger, D.N. Gastroenterology 89:6–12, 1985.PubMedGoogle Scholar
  28. 28.
    Manning, A.S., Bernier M., Hearse, D.J. J. Mol. Cell. Cardiol. (in press)Google Scholar

Copyright information

© Kluwer Academic Publishers 1988

Authors and Affiliations

  • James M. Downey
    • 1
  • Lynne J. Eddy
    • 1
  • Chiaki Shirato
    • 1
  • Patricia Molina
    • 1
  • Miguel Molina
    • 1
  1. 1.Department of Physiology, College of MedicineUniversity of South AlabamaMobileUSA

Personalised recommendations