, Volume 14, Issue 4, pp 409–419 | Cite as

Reactivity of active center analogs of Cu2Zn2 superoxide dismutase on activated polymorphonuclear leukocytes

  • Ralf Miesel
  • Hans-Jürgen Hartmann
  • Yuejin Li
  • Ulrich Weser
Original Articles


In unseparated human blood the Cu2Zn2 superoxide dismutase mimetic reactivity of several differently coordinated low Mr copper chelates on TPA-activated polymorphonuclear leukocytes was evaluated and compared to their apo-chelates, CuSO4, and the native enzyme. Similar to intact superoxide dismutase, 350–400 nM Cu flexibly complexed in a di-Schiff base mode in CuPu(Py)2 and CuPu(Im)2, respectively, was sufficient to inhibit the oxidative burst-dependent superoxide production of human blood phagocytes by 50%. Acetate-or biuret-type copper chelates behaved like CuSO2. The catalytic superoxide dismuting reactivity of the di-Schiff base active center analogs of SOD was confirmed using isolated porcine PMNs. Even in the presence of 600μM albumin as a model for competitive copper chelation in biological fluids CuPu(Py)2 and CuPu(Im)2 remained active. The stability during the Cu(I)/Cu(II) redox cycling was demonstrated in the presence of activated PMNs and albumin, taking advantage of the electron paramagnetic properties of CuPu(Py)2 and CuPu(Im)2.


Albumin Superoxide Superoxide Dismutase Human Blood CuSO4 
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  1. 1.
    Younes, M., E. Lengfelder, S. Zienau, andU. Weser. 1978. Pulseradiolytically generated superoxide and Cu(II)-salicylates.Biochem. Biophys. Res. Commun. 81:576–580.Google Scholar
  2. 2.
    Weser, U., L. M. Schubotz, andE. Lengfelder. 1982. Imidazole-bridged copper complexes as Cu2Zn2 superoxide dismutase models.J. Mol. Cat. 3:249–261.Google Scholar
  3. 3.
    Linss, M., andU. Weser. 1987. Redox behaviour and stability of active centre analogues of Cu2Zn2 superoxide dismutase.Inorg. Chim. Acta 138:175–178.Google Scholar
  4. 4.
    Linss, M., andU. Weser. 1986. The di-Schiff base of pyridine-2-aldehyde and 1,4-diaminobutane, a flexible Cu(I)/Cu(II) chelator of significant superoxide mimetic activity.Inorg. Chim. Acta 125:117–121.Google Scholar
  5. 5.
    Brigelius, R., R. Spöttle, W. Bors, E. Lengfelder, M. Saran, andU. Weser. 1974. superoxide dismtutase activity of low molecular weight Cu2+-chelates studied by pulseradiolysis.FEBS Lett. 47:72–75.Google Scholar
  6. 6.
    Brigelius, R., H. J. Hartmann, W. Bors, M. Saran, E. Lengfelder, andU. Weser. 1975. superoxide dismutase activity of Cu(Tyr)2 and Cu, Co-erythrocuprein. Z.Physiol. Chem. 356:739–745.Google Scholar
  7. 7.
    Lan, S., andB. Sarkar. 1971. Ternary coordination complexes between human serum albumin, copper (II) and L-histidine.J. Biol. Chem. 246:5938–5943.Google Scholar
  8. 8.
    Miesel, R., andU. Weser. 1989. Reactivity of active centre analogues of Cu2Zn2 superoxide dismutase during the aqueous decay of K3CrO8.Inorg. Chim. Acta 160:119–121.Google Scholar
  9. 9.
    Hangarter, W. 1982. Copper-salicylate in rheumatoid and similar degenerative diseasesIn Inflammatory Diseases and Copper, J.R.J. Sorenson, editor. Humana Press, Clifton, New Jersey, 439–449.Google Scholar
  10. 10.
    Sorenson, J. R. J. 1976. Copper chelates as possible active forms of the antiarhtritic agents.J. Med. Chem. 19:135–148.Google Scholar
  11. 11.
    Carson, S., E. E. Vogin, W. Huber, andT. L. Schulte. 1973. Safety tests of orgotein, an antiinflammatory protein.Toxicol. Appl. Pharmacol. 26:184–202.Google Scholar
  12. 12.
    Klebanoff, S. J. 1982.In Advances in Host Defense Mechanisms, Vol. I. J.J. Gallin and A.S. Fanci, editor. Raven Press, New York. 111–162.Google Scholar
  13. 13.
    Yasaka, T., L. A. Boxer, andR. L. Baschner. 1982. Monocyte aggregation and superoxide anion release in response to FMLP and PAF.J. Immunol. 128:1939–1944.Google Scholar
  14. 14.
    Rossi, F., V. Della Bianca, andP. De Togni. 1985. Mechanisms and functions of the oxygen radicals producing respiration of phagocytes.Comp. Immunol. Microbiol. Infect. Dis. 8:187–204.Google Scholar
  15. 15.
    Dal Maestro, R. F., K. E. Arfors, J. Bjork, andM. Planker. 1980.In Biological and Clinical Aspects of superoxide and superoxide Dismutase. W. H. Banister and J. V. Bannister, editors. Elsevier, Amsterdam. 127–140.Google Scholar
  16. 16.
    Babior, B. M. 1984. The repiratory burst of phagocytesJ. Clin. Invest. 73:599–601.Google Scholar
  17. 17.
    Hartmann, H. J., A. Gärtner, andU. Weser. 1985. Copper dependent control of the enzymic and phagocyte induced degradation of some biopolymers, a possible link to systemic inflammation.Clin. Chim. Acta 152:95–103.Google Scholar
  18. 18.
    Flohe, L., H. Giertz, andR. Beckmann. 1985.In Handbook of Inflammation, Vol. 5, The Pharmacology of Inflammation. I. L. Bonta, M. A. Bray, and M. J. Parnham, editors. Elsevier, Amsterdam. 255–281.Google Scholar
  19. 19.
    Goldstein, S., andG. Czapski. 1987. Mechanism of reduction of bleomycin-Cu(II) by CO2 and oxidation of bleomycin-Cu(I) by H2O2 in the absence and presence of DNA.Int. J. Radiat. Biol. 51:693–706.Google Scholar
  20. 20.
    Kreisl, C., andE. Lengfelder. 1984. Hyaluronic acid degradation by reactions producing activated oxygen species.Life Chem. Rep. 2:81–84.Google Scholar
  21. 21.
    Badwey, J. A., andM. L. Karnovsky. 1980. Active oxygen species and the functions of phagocytic leucocytes.Annu. Rev. Biochem. 49:695–726.Google Scholar
  22. 22.
    Allen, R. C. 1980.In The Reticuloendothelial System, Vol. II. A. J. Sbarra and R. R. Strauss, editors. Plenum, New York. 309.Google Scholar
  23. 23.
    Deuschle, U., andU. Weser. 1985. Copper and inflammation.Prog. Clin. Biochem. Med. 2:97–130.Google Scholar
  24. 24.
    De Alvare, L. R., K. Goda, andT. Kimura. 1976. Mechanism of superoxide anion scavenging reaction by bis(-salicylato)-copper (II) complex.Biochem. Biophys. Res. Commun. 69:687–694.Google Scholar
  25. 25.
    Schechinger, T., W. Hiller, C. Maichle, J. Strähle, andU. Weser. 1988. A five coordinate copper complex with superoxide dismutase mimetic activity from Streptomyces antibioticus.Biol. Methods 1:112–116.Google Scholar
  26. 26.
    Allen, R.C. 1982.In Chemical and Biological Generation of Excited States. W. Adam and G. Cilento, editors. Academic Press, New York. 209–344.Google Scholar
  27. 27.
    Allen, R. C., andL. D. Loose. 1976. Phagocytic activation of a luminol-dependent chemiluminescence in rabbit alveolar and peritoneal macrophages.Biochem. Biophys. Res. Commun. 69:245–252.Google Scholar
  28. 28.
    Allen, R. C. 1972. Evidence for the generation of an electronic excitation state in human polymorphonuclear leucocytes and its participation in bactericidal activity.Biochem. Biophys. Res. Commun. 47:679–684.Google Scholar
  29. 29.
    Tainer, J. A., E. D. Getzoff, J. S. Richardson, andD. C. Richardson. 1983. Structure and mechanism of copper, zinc superoxide dismutase.Nature 306:284–286.Google Scholar
  30. 30.
    Miesel, R., andU. Weser. 1988. superoxide dismutase mimetic activity of low Mr copper chelates.Biol. Chem. Hoppe-Seyler 369:877.Google Scholar
  31. 31.
    Müller-Peddinghaus, R., andM. Wurl. 1987. The amplified chemiluminescence test to characterize antirheumatic drugs as oxygen radical scavengers.Biochem, Pharmacol. 36:1125–1132.Google Scholar
  32. 32.
    Miesel, R., H. J. Hartmann, andU. Weser. 1989. Copper (I)-thionein and inflammation.Biol. Chem. Hoppe-Seyler 370:935–936.Google Scholar
  33. 33.
    Rotilio, G., A. Rigo, P. Viglino, andL. Calabrese. 1977.In: superoxide and superoxide Dismutases. A. M. Michelson, J. M. McCord, and I. Fridovich, editors. Academic Press, London. 207–214.Google Scholar
  34. 34.
    Weser, U., R. Miesel, H. J. Hartmann, andW. Heizmann. 1989. Mummified enzymes.Nature 341:696.Google Scholar

Copyright information

© Plenum Publishing Corporation 1990

Authors and Affiliations

  • Ralf Miesel
    • 1
  • Hans-Jürgen Hartmann
    • 1
  • Yuejin Li
    • 1
  • Ulrich Weser
    • 1
  1. 1.Anorganische Biochemie Physiologisch-Chemisches InstitutUniversität TübingenTübingenF.R.G.

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