Skip to main content
SpringerLink
Log in
Book cover

Biological Reactive Intermediates V pp 147–161Cite as

The Importance of Superoxide in Nitric Oxide-Dependent Toxicity

Evidence for Peroxynitrite-Mediated Injury

  • Chapter

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 387))

Abstract

The potent vasodilator effects of pharmacological agents such as nitroglycerin have been known for over 100 years. In the last 20 years evidence has accumulated suggesting that nitric oxide is the species responsible for the biological effects of nitro-vasodilators. However, only within the last 10 years has the importance of earlier studies become clear; nitric oxide is an enzymatically-produced second messenger. Work of atmospheric chemists would indicate that nitrogen oxides like nitric oxide are harmful, yet we live out our lives constantly generating nitric oxide in endothelial cells and neurons and pharmacologic doses of nitro-vasodilators are devoid of overt toxicity. Furthermore, at physiologically relevent concentrations, no direct toxicity of nitric oxide itself has been demonstrated. Nontheless, endogenous production of nitric oxide has been implicated in reoxygenation injury following ischemia (1,2), glutamate-mediated neuronal toxicity (2,3), inflammation (4–6) and graft versus host disease (7–9). How then, can nitric oxide be injurious?

Invited paper

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Masini, E., Bianchi, S., Mugnai, L., Gambassi, F., Lupini, M., Pistelli, A., and Mannaioni, P.F. 1991. The effect of nitric oxide generators on ischemia reperfusion injury and histamine release in isolated perfused guinea-pig heart. Agents & Actions 33: 53–56.

    Article  CAS  Google Scholar 

  2. Cazevieille, C., Muller, A., Meynier, F., and Bonne, C. 1993. Superoxide and nitric oxide cooperation in hypoxia/reoxygenation-induced neuron injury. Free Radical Biology & Medicine 14: 389–395.

    Article  CAS  Google Scholar 

  3. Dawson, V. L., Dawson, T.M., Bartley, D.A., Uhl, G.R., and Snyder, S.H. 1993. Mechanisms of nitric oxide-mediated neurotoxicity in primary brain cultures. Journal of Neuroscience 13: 2651–2661.

    PubMed  CAS  Google Scholar 

  4. Green, S. J., Mellouk, S., Hoffman, S.L., Meltzer, M.S., and Nacy, C.A. 1990. Cellular mechanisms of nonspecific immunity to intracellular infection: cytokine-induced synthesis of toxic nitrogen oxides from L-arginine by macrophages and hepatocytes. Immunology Letters 25: 15–19.

    Article  PubMed  CAS  Google Scholar 

  5. Mulligan, M. S., Hevel, J.M., Marietta, M.A., and Ward, P.A. 1991. Tissue injury caused by deposition of immune complexes is L-arginine dependent. Proceedings of the National Academy of Sciences of the United States of America 88: 6338–6342.

    Article  PubMed  CAS  Google Scholar 

  6. Billiar, T. R., Hoffman, R.A., Curran, R.D., Langrehr, J.M., and Simmons, R.L. 1992. Arole for inducible nitric oxide biosynthesis in the liver in inflammation and in the allogeneic immune response. [Review]. Journal of Laboratory & Clinical Medicine 120: 192–197.

    CAS  Google Scholar 

  7. Hoffman, R. A., Langrehr, J.M., and Simmons, R.L. 1992. The role of inducible nitric oxide synthetase during graft-versus-host disease. Transplantation Proceedings 24: 2856.

    PubMed  CAS  Google Scholar 

  8. Garside, P., Hutton, A.K., Severn, A., Liew, F.Y., and Mowat, A.M. 1992. Nitric oxide mediates intestinal pathology in graft-vs.-host disease. European Journal of Immunology 22: 2141–2145.

    Article  PubMed  CAS  Google Scholar 

  9. Langrehr, J. M., Murase, N., Markus, P.M., Cai, X., Neuhaus, P., Schraut, W., Simmons, R.L., and Hoffman, R.A. 1992. Nitric oxide production in host-versus-graft and graft-versus-host reactions in the rat. Journal of Clinical Investigation 90: 679–683.

    Article  PubMed  CAS  Google Scholar 

  10. Huie, R. E. and Padmaja, S. 1993. The reaction of NO with Superoxide. Free Radical Research Communications 18: 195–199.

    Article  PubMed  CAS  Google Scholar 

  11. Mittal, C. K. and Murad, F. 1977. Activation of guanylate cyclase by Superoxide dismutase and hydroxyl radical: A physiological regulator of guanosine 3’,5’-monophosphate formation. Proc. Natl. Acad. Sci. U. S. A. 74: 4360–4364.

    Article  PubMed  CAS  Google Scholar 

  12. Craven, P. A. and DeRubertis, F.R. 1978. Restoration of the responsiveness of purified guanylate cyclase to nitrosoguanidine, nitric oxide, and related activators by heme and hemeproteins. Evidence for involvement of the paramagnetic nitrosyl-heme complex in enzyme activation. J. Biol. Chem. 253: 8433–8443.

    PubMed  CAS  Google Scholar 

  13. Ignarro, L. J., Adams, J.B., Horwitz, P.M., and Wood, K.S. 1986. Activation of soluble guanylate cyclase by NO-hemoproteins involves NO-heme exchange. Comparison of heme-containing and heme-deficient enzyme forms., J. Biol. Chem. 261: 4997–5002.

    PubMed  CAS  Google Scholar 

  14. Sessa. W. C. 1994. The nitric oxide synthase family of proteins. [Review]. Journal of Vascular Research 31: 131–143.

    Article  PubMed  CAS  Google Scholar 

  15. Murad, F., Mittal, C.K., Arnold, W.P., Katsuki, S., and Kimura, H. 1978. Guanylate cyclase: Activation by azide, nitro compounds, nitric oxide, and hydroxyl radical and inhibition by hemoglobin and myoglobin. Adv. Cyclic. Nucleotide. Res. 9: 145–158.

    PubMed  CAS  Google Scholar 

  16. Shibuki, K. 1990. An electrochemical microprobe for detecting nitric oxide release in brain tissue. Neuroscience Research 9: 69–76.

    Article  PubMed  CAS  Google Scholar 

  17. Hauschildt, S., Luckhoff, A., Mulsch, A., Kohler, J., Bessler, W., and Busse, R. 1990. Induction and activity of NO synthase in bone-marrow-derived macrophages are independent of Ca2+. Biochem. J. 270: 351–356.

    PubMed  CAS  Google Scholar 

  18. Knowles, R. G., Merrett, M., Salter, M., and Moncada, S. 1990. Differential induction of brain, lung and liver nitric oxide synthase by endotoxin in the rat. Biochem. J. 270: 833–836.

    PubMed  CAS  Google Scholar 

  19. Busse, R. and Mulsch, A. 1990. Induction of nitric oxide synthase by cytokines in vascular smooth muscle cells. FEBS. Lett. 275: 87–90.

    Article  PubMed  CAS  Google Scholar 

  20. Corbett, J. A., Lancaster, J.R., Jr., Sweetland, M.A., and McDaniel, M.L. 1991. Interleukin-1 beta-induced formation of EPR-detectable iron-nitrosyl complexes in islets of Langerhans. Role of nitric oxide in interleukin-1 beta-induced inhibition of insulin secretion. J. Biol. Chem. 266: 21351–21354.

    PubMed  CAS  Google Scholar 

  21. Stuehr, D. J., Cho, HJ., Kwon, N.S., Weise, M.F., and Nathan, CF. 1991. Purification and characterization of the cytokine-induced macrophage nitric oxide synthase: An FAD-and FMN-containing flavoprotein. Proc. Natl. Acad. Sci. U. S. A. 88: 7773–7777.

    Article  PubMed  CAS  Google Scholar 

  22. Mollace, V., Colasanti, M., Rodino, P., Massoud, R., Lauro, G.M., and Nistico, G. 1993. Cytokine-induced nitric oxide generation by cultured astrocytoma cells involves Ca(++)-calmodulin-independent NO-synthase. Biochemical & Biophysical Research Communications 191: 327–334.

    Article  CAS  Google Scholar 

  23. Malinski, T., Bailey, F., Zhang, Z.G., and Chopp, M. 1993. Nitric oxide measured by a porphyrinic microsensor in rat brain after transient middle cerebral artery occlusion. Journal of Cerebral Blood Flow & Metabolism 13: 355–358.

    Article  CAS  Google Scholar 

  24. Welsh, N., Eizirik, D.L., Bendtzen, K., and Sandier, S. 1991. Interleukin-1 beta-induced nitric oxide production in isolated rat pancreatic islets requires gene transcription and may lead to inhibition of the Krebs cycle enzyme aconitase. Endocrinology 129: 3167–3173.

    Article  PubMed  CAS  Google Scholar 

  25. Kwon, N. S., Stuehr, D.J., and Nathan, C.F. 1991. Inhibition of tumor cell ribonucleotide reductase by macrophage-derived nitric oxide. Journal of Experimental Medicine 174: 761–767.

    Article  PubMed  CAS  Google Scholar 

  26. Lepoivre, M., Fieschi, F., Coves, J., Thelander, L., and Fontecave, M. 1991. Inactivation of ribonucleotide reductase by nitric oxide. Biochemical & Biophysical Research Communications 179: 442–448.

    Article  CAS  Google Scholar 

  27. Wink, D. A., Kasprzak, K.S., Maragos, CM., Elespuru, R.K., Misra, M., Dunams, T.M., Cebula, T.A., Koch, W.H., Andrews, A.W., Allen, J.S., et al. 1991. DNA deaminating ability and genotoxicity of nitric oxide and its progenitors. Science 254: 1001–1003.

    Article  PubMed  CAS  Google Scholar 

  28. Nguyen, T., Brunson, D., Crespi, C.L., Penman, B.W., Wishnok, J.S., and Tannenbaum, S.R. 1992. DNA damage and mutation in human cells exposed to nitric oxide in vitro. Proceedings of the National Academy of Sciences of the United States of America 89: 3030–3034.

    Article  PubMed  CAS  Google Scholar 

  29. Green, S. J., Meltzer, M.S., Hibbs, J.B., Jr., and Nacy, C.A. 1990. Activated macrophages destroy intracellular Leishmania major amastigotes by an L-arginine-dependent killing mechanism. Journal of Immunology 144: 278–283.

    CAS  Google Scholar 

  30. Oswald, I. P., Wynn, T.A., Sher, A., and James, S.L. 1994. NO as an effector molecule of parasite killing: Modulation of its synthesis by cytokines. [Review]. Comparative Biochemical Physiological Pharmacological and Toxicological Endocrinology 108: 11–18.

    Article  CAS  Google Scholar 

  31. Boveris, A., Cadenas, E., and Stoppani, A.O.M. 1976. Role of ubiquinone in the mitochondrial generation of hydrogen peroxide. Biochem. J. 156: 435–444.

    PubMed  CAS  Google Scholar 

  32. Turrens, J. F. and Boveris, A. 1980. Generation of Superoxide anion by the NADH dehydrogenase of bovine heart mitochondria. Biochem. J. 191: 421–427.

    PubMed  CAS  Google Scholar 

  33. Boveris, A. and Chance, B. 1973. The mitochondrial generation of hydrogen peroxide: General properties and effect of hyperbaric oxygen. Biochem. J. 134: 707–716.

    PubMed  CAS  Google Scholar 

  34. Cross, A. R. and Jones, O.T.G. 1991. Enzymic mechanisms of Superoxide production. Biochim. Biophys. Acta Bio-Energetics 1057: 281–298.

    Article  CAS  Google Scholar 

  35. Gardner, P. R. and Fridovich, I. 1991. Superoxide sensitivity of the Escherichia coli 6-phosphogluconate dehydratase. Journal of Biological Chemistry 266: 1478–1483.

    PubMed  CAS  Google Scholar 

  36. Pauling, L. 1979. The discovery of the Superoxide radical. Trends in Biochemical Sciences 4: N270–N271.

    Article  CAS  Google Scholar 

  37. Sawyer, D. T. and Valentine, J.S. 1981. How super is Superoxide? Accts. Chem. Res. 14: 393–400.

    Article  CAS  Google Scholar 

  38. Bielski, B. H. J. 1978. Re-evaluation of the spectral and kinetic properties of HO2 and O2⨪ free radicals. Photochem. Photobiol. 28: 645–649.

    Article  CAS  Google Scholar 

  39. Mccord, J. M. and Fridovich, I. 1969. Superoxide dismutase: An enzymic function for erythrocuprein (hemocuprein). J. Biol Chem. 244: 6049–6055.

    PubMed  CAS  Google Scholar 

  40. Biemond, P., van Eijk, H.G., Swaak, A.J.G., and Koster, J.F. 1984. Iron mobilization from ferritin by Superoxide derived from phagocytosing polymorphonuclear leucocytes. Possible mechanism in inflammation diseases. J. Clin. Invest. 73: 1576–1579.

    Article  PubMed  CAS  Google Scholar 

  41. Thomas, C. E., Morehouse, L.A., and Aust, S.D. 1985. Ferritin and superoxide-dependent lipid peroxidation. J. Biol. Chem. 260: 3275–3280.

    PubMed  CAS  Google Scholar 

  42. Klug, D., Rabani, J., and Fridovich, I. 1972. A direct demonstration of the catalytic action of Superoxide dismutase through the use of pulse radiolysis. J. Biol. Chem. 247: 4839–4842.

    PubMed  CAS  Google Scholar 

  43. Haber, F. and Weiss, J. 1934. The catalytic decomposition of hydrogen peroxide by iron salts. Proc.Roy.Soc. 147: 332–351.

    Article  CAS  Google Scholar 

  44. Gutteridge, J. M. C. 1984. Lipid peroxidation initiated by superoxide-dependent hydroxyl radicals using complexed iron and hydrogen peroxide. FEBS Lett. 172: 245–249.

    Article  PubMed  CAS  Google Scholar 

  45. Wang, Q. J., Giri, S.N., Hyde, D.M., and Li, C.F. 1991. Amelioration of bleomycin-induced pulmonary fibrosis in hamsters by combined treatment with taurine and niacin. Biochem. Pharmacol. 42: 1115–1122.

    Article  PubMed  CAS  Google Scholar 

  46. Beckman, J. S., Beckman, T.W., Chen, J., Marshall, P.A., and Freeman, B.A. 1990. Apparent hydroxyl radical production by peroxynitrite: Implications for endothelial injury from nitric oxide and Superoxide. Proc. Natl Acad. Sci. U. S. A. 87: 1620–1624.

    Article  PubMed  CAS  Google Scholar 

  47. Koppenol, W. H., Moreno, J.J., Pryor, W.A., Ischiropoulos, H., and Beckman, J.S. 1992. Peroxynitrite, a cloaked oxidant formed by nitric oxide and Superoxide. Chemical Research in Toxicology 5: 834–842.

    Article  PubMed  CAS  Google Scholar 

  48. Crow, J. P., Spruell, C, Chen, J., Gunn, C, Ischiropoulos, H., Tsai, M., Smith, C.D., Radi, R., Koppenol, W.H., and Beckman, J.S. 1994. On the pH-dependent yield of hydroxyl radical products from peroxynitrite. Free Radical Biology & Medicine 16: 331–338.

    Article  CAS  Google Scholar 

  49. Halfpenny, E. and Robinson, P.L. 1952. The nitration and hydroxylation of aromatic compounds by pernitrous acid. J. Chem. Soc. 16 939–946.

    Article  Google Scholar 

  50. Ischiropoulos, H., Zhu, L., Chen, J., Tsai, M., Martin, J.C, Smith, C.D., and Beckman, J.S. 1992. Peroxynitrite-mediated tyrosine nitration catalyzed by Superoxide dismutase. Archives of Biochemistry & Biophysics 298: 431–437.

    Article  CAS  Google Scholar 

  51. van der Vliet, A., O’Neill, CA., Halliwell, B., Cross, C.E., and Kaur, H. 1994. Aromatic hydroxylation and nitration of phenylalanine and tyrosine by peroxynitrite. Evidence for hydroxyl radical production from peroxynitrite. FEBS Letters. 339: 89–92.

    Article  PubMed  Google Scholar 

  52. Radi, R., Beckman, J.S., Bush, K.M., and Freeman, B.A. 1991. Peroxynitrite-induced membrane lipid peroxidation: The cytotoxic potential of Superoxide and nitric oxide. Archives of Biochemistry & Biophysics 288: 481–487.

    Article  CAS  Google Scholar 

  53. Moreno, J. J. and Pryor, W.A. 1992. Inactivation of alpha 1-proteinase inhibitor by peroxynitrite. Chemical Research in Toxicology 5: 425–431.

    Article  PubMed  CAS  Google Scholar 

  54. Bauer, M. L., Beckman, J.S., Bridges, R.J., Fuller, CM., and Matalon, S. 1992. Peroxynitrite inhibits sodium uptake in rat colonic membrane vesicles. Biochim. Biophys. Acta. 1104: 87–94.

    Article  PubMed  CAS  Google Scholar 

  55. King, P. A., Anderson, V.E., Edwards, J.O., Gustafson, G., Plumb, R.C, and Suggs, J.W. 1992. A stable solid that generates hydroxyl radical upon dissolution in aqueous solution: Reaction with proteins and nucleic acid. J. Am. Chem. Soc. 114: 5430–5432.

    Article  CAS  Google Scholar 

  56. Radi, R., Beckman, J.S., Bush, K.M., and Freeman, B.A. 1991. Peroxynitrite oxidation of sulfhydryls. The cytotoxic potential of Superoxide and nitric oxide. J. Biol. Chem. 266: 4244–4250.

    PubMed  CAS  Google Scholar 

  57. Rubbo, H., Denicola, A., and Radi, R. 1994. Peroxynitrite inactivates thiol-containing enzymes of Trypanosoma cruzi energetic metabolism and inhibits cell respiration. Archives of Biochemistry & Biophysics 308: 96–102.

    Article  CAS  Google Scholar 

  58. Hofman, M. A. 1991. From Here to Eternity. Brain Ageing in an Evolutionary Perspective. Neurobiol. Aging. 12: 338–340.

    Article  PubMed  CAS  Google Scholar 

  59. Beckman, J. S., Ischiropoulos, H., Zhu, L., van der Woerd, M., Smith, C, Chen, J., Harrison, J., Martin, J.C, and Tsai, M. 1992. Kinetics of Superoxide dismutase-and iron-catalyzed nitration of phenolics by peroxynitrite. Archives of Biochemistry & Biophysics 298: 438–445.

    Article  CAS  Google Scholar 

  60. Bates, J. N., Harrison, D.G., Myers, P.R., and Minor, R.L. 1991. EDRF: Nitrosylated compound or authentic nitric oxide. Basic Research In Cardiology 86 Suppl 2: 17–26.

    PubMed  Google Scholar 

  61. Chen, F. Y. and Lee, T.J. 1993. Role of nitric oxide in neurogenic vasodilation of porcine cerebral artery. Journal of Pharmacology & Experimental Therapeutics 265: 339–345.

    CAS  Google Scholar 

  62. Beckman, J. S., Ye, Y.Z., Anderson, P.G., Chen, J., Accavitti, M.A., Tarpey, M.M., and White, C.R. 1994. Extensive nitration of protein tyrosines in human atherosclerosis detected by immunohistochemistry. Biological Chemistry Hoppe-Seyler 375: 81–88.

    Article  Google Scholar 

  63. Martin, B. L., Wu, D., Jakes, S., and Graves, D.J. 1990. Chemical influences on the specificity of tyrosine phosphorylation. Journal of Biological Chemistry 265: 7108–7111.

    PubMed  CAS  Google Scholar 

  64. Chantier, P. D. and Gratzer, W.B. 1975. Effects of specific chemical modification of actin. European Journal of Biochemistry 60: 67–72.

    Article  Google Scholar 

  65. Feste, A. and Gan, J.C. 1981. Selective loss of elastase inhibitory activity of alpha 1-proteinase inhibitor upon chemical modification of its tyrosyl residues. Journal of Biological Chemistry 256: 6374–6380.

    PubMed  CAS  Google Scholar 

  66. Chacko, G. K. 1985. Modification of human high density lipoprotein (HDL3) with tetranitromethane and the effect on its binding to isolated rat liver plasma membranes. Journal of Lipid Research 26: 745–754.

    PubMed  CAS  Google Scholar 

  67. Deckers-Hebestreit, G., Schmid, R., Kiltz, H.H., and Altendorf, K. 1987. F0 portion of Escherichia coli ATP synthase: Orientation of subunit c in the membrane. Biochemistry 26: 5486–5492.

    Article  PubMed  CAS  Google Scholar 

  68. Lundblad, R. L., Noyes, C.M., Featherstone, G.L., Harrison, J.H., and Jenzano, J.W. 1988. The reaction of bovine alpha-thrombin with tetranitromethane. Characterization of the modified protein. Journal of Biological Chemistry 263: 3729–3734.

    PubMed  CAS  Google Scholar 

  69. Tawfik, D. S., Chap, R., Eshhar, Z., and Green, B.S. 1994. pH on-off switching of antibody-hapten binding by site-specific chemical modification of tyrosine. Protein Engineering 7: 431–434.

    Article  PubMed  CAS  Google Scholar 

  70. Nixon, R. A. 1993. The regulation of neurofilament protein dynamics by phosphorylation: clues to neurofibrillary pathobiology. [Review]. Brain Pathology 3: 29–38.

    Article  PubMed  CAS  Google Scholar 

  71. Stork, G., Suh, H.S., and Kim, G. 1991. The temporary silicon connection method in the control of regiochemistry and stereochemistry: Applications to radical-mediated reactions — The stereospecific synthesis of C-glycosides. J. Am. Chem. Soc. 113: 7054–7056.

    Article  CAS  Google Scholar 

  72. Schuchmann, M.N., Schuchmann, H.P., Hess, M., and Vonsonntag, C. 1991. O2.−Addition to ketomalonate leads to decarboxylation: A chain reaction in oxygenated aqueous solution. J. Am. Chem. Soc. 113: 6934–6937.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anesthesiology, THT 958, University of Alabama at Birmingham, 619 19th Street South, Birmingham, Alabama, 35233-1924, USA

    John P. Crow & Joseph S. Beckman

Authors
  1. John P. Crow
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joseph S. Beckman
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, New Jersey, USA

    Robert Snyder  & Charlotte M. Witmer  & 

  2. University of Arizona, Tuscon, Arizona, USA

    I. Glenn Sipes

  3. Medical University of South Carolina, Charleston, South Carolina, USA

    David J. Jollow

  4. University of Texas, Austin, Texas, USA

    Terrence J. Monks

  5. Thomas Jefferson University, Philadelphia, Pennsylvania, USA

    James J. Kocsis  & George F. Kalf  & 

  6. GSF Institute of Toxicology, Technical University, Munich, Germany

    Helmut Greim

Rights and permissions

Reprints and permissions

Copyright information

© 1996 Springer Science+Business Media New York

About this chapter

Cite this chapter

Crow, J.P., Beckman, J.S. (1996). The Importance of Superoxide in Nitric Oxide-Dependent Toxicity. In: Snyder, R., et al. Biological Reactive Intermediates V. Advances in Experimental Medicine and Biology, vol 387. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9480-9_21

Download citation

  • DOI: https://doi.org/10.1007/978-1-4757-9480-9_21

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4757-9482-3

  • Online ISBN: 978-1-4757-9480-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation