Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1994 Oct 1;303(Pt 1):295–301. doi: 10.1042/bj3030295

Interactions of peroxynitrite with human plasma and its constituents: oxidative damage and antioxidant depletion.

A Van der Vliet 1, D Smith 1, C A O'Neill 1, H Kaur 1, V Darley-Usmar 1, C E Cross 1, B Halliwell 1
PMCID: PMC1137590  PMID: 7945255

Abstract

Endothelial cells and activated phagocytes produce both nitric oxide (.NO) and superoxide (O2.-), which react to form peroxynitrite. Peroxynitrite has been suggested to be directly cytotoxic and also to decompose into other toxic species. In order to understand the consequences of peroxynitrite generation in vivo, we examined its reaction with human blood plasma. Peroxynitrite decreased the total peroxyl-trapping capacity of plasma. In terms of specific antioxidants, addition of peroxynitrite to plasma leads to rapid oxidation of ascorbic acid, uric acid and plasma SH groups. The oxidation of plasma SH groups was enhanced in dialysed plasma and returned to control levels by the addition of physiological levels of bicarbonate. Evidence was found for formation of nitro-adducts to aromatic side chains in plasma proteins by peroxynitrite. Peroxynitrite also leads to depletion of ubiquinol and formation of traces of lipid hydroperoxides in plasma, although alpha-tocopherol levels were only slightly decreased. Peroxynitrite formation in human body fluids is likely to cause antioxidant depletion and oxidative damage.

Full text

PDF
295

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amadò R., Aeschbach R., Neukom H. Dityrosine: in vitro production and characterization. Methods Enzymol. 1984;107:377–388. doi: 10.1016/0076-6879(84)07026-9. [DOI] [PubMed] [Google Scholar]
  2. Babior B. M. Oxygen-dependent microbial killing by phagocytes (first of two parts). N Engl J Med. 1978 Mar 23;298(12):659–668. doi: 10.1056/NEJM197803232981205. [DOI] [PubMed] [Google Scholar]
  3. Beckman J. S., Beckman T. W., Chen J., Marshall P. A., Freeman B. A. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci U S A. 1990 Feb;87(4):1620–1624. doi: 10.1073/pnas.87.4.1620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Beckman J. S., Ischiropoulos H., Zhu L., van der Woerd M., Smith C., Chen J., Harrison J., Martin J. C., Tsai M. Kinetics of superoxide dismutase- and iron-catalyzed nitration of phenolics by peroxynitrite. Arch Biochem Biophys. 1992 Nov 1;298(2):438–445. doi: 10.1016/0003-9861(92)90432-v. [DOI] [PubMed] [Google Scholar]
  5. Beckmann J. S., Ye Y. Z., Anderson P. G., Chen J., Accavitti M. A., Tarpey M. M., White C. R. Extensive nitration of protein tyrosines in human atherosclerosis detected by immunohistochemistry. Biol Chem Hoppe Seyler. 1994 Feb;375(2):81–88. doi: 10.1515/bchm3.1994.375.2.81. [DOI] [PubMed] [Google Scholar]
  6. Buettner G. R. The pecking order of free radicals and antioxidants: lipid peroxidation, alpha-tocopherol, and ascorbate. Arch Biochem Biophys. 1993 Feb 1;300(2):535–543. doi: 10.1006/abbi.1993.1074. [DOI] [PubMed] [Google Scholar]
  7. Carreras M. C., Pargament G. A., Catz S. D., Poderoso J. J., Boveris A. Kinetics of nitric oxide and hydrogen peroxide production and formation of peroxynitrite during the respiratory burst of human neutrophils. FEBS Lett. 1994 Mar 14;341(1):65–68. doi: 10.1016/0014-5793(94)80241-6. [DOI] [PubMed] [Google Scholar]
  8. Cotgreave I. A., Moldéus P. Methodologies for the application of monobromobimane to the simultaneous analysis of soluble and protein thiol components of biological systems. J Biochem Biophys Methods. 1986 Nov;13(4-5):231–249. doi: 10.1016/0165-022x(86)90102-8. [DOI] [PubMed] [Google Scholar]
  9. Darley-Usmar V. M., Hogg N., O'Leary V. J., Wilson M. T., Moncada S. The simultaneous generation of superoxide and nitric oxide can initiate lipid peroxidation in human low density lipoprotein. Free Radic Res Commun. 1992;17(1):9–20. doi: 10.3109/10715769209061085. [DOI] [PubMed] [Google Scholar]
  10. Denicola A., Rubbo H., Rodríguez D., Radi R. Peroxynitrite-mediated cytotoxicity to Trypanosoma cruzi. Arch Biochem Biophys. 1993 Jul;304(1):279–286. doi: 10.1006/abbi.1993.1350. [DOI] [PubMed] [Google Scholar]
  11. Driskell W. J., Neese J. W., Bryant C. C., Bashor M. M. Measurement of vitamin A and vitamin E in human serum by high-performance liquid chromatography. J Chromatogr. 1982 Sep 10;231(2):439–444. doi: 10.1016/s0378-4347(00)81869-1. [DOI] [PubMed] [Google Scholar]
  12. ELLMAN G. L. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959 May;82(1):70–77. doi: 10.1016/0003-9861(59)90090-6. [DOI] [PubMed] [Google Scholar]
  13. Frei B., England L., Ames B. N. Ascorbate is an outstanding antioxidant in human blood plasma. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6377–6381. doi: 10.1073/pnas.86.16.6377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Frei B., Kim M. C., Ames B. N. Ubiquinol-10 is an effective lipid-soluble antioxidant at physiological concentrations. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4879–4883. doi: 10.1073/pnas.87.12.4879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Frei B., Stocker R., Ames B. N. Antioxidant defenses and lipid peroxidation in human blood plasma. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9748–9752. doi: 10.1073/pnas.85.24.9748. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Frei B., Yamamoto Y., Niclas D., Ames B. N. Evaluation of an isoluminol chemiluminescence assay for the detection of hydroperoxides in human blood plasma. Anal Biochem. 1988 Nov 15;175(1):120–130. doi: 10.1016/0003-2697(88)90369-7. [DOI] [PubMed] [Google Scholar]
  17. Graham A., Hogg N., Kalyanaraman B., O'Leary V., Darley-Usmar V., Moncada S. Peroxynitrite modification of low-density lipoprotein leads to recognition by the macrophage scavenger receptor. FEBS Lett. 1993 Sep 13;330(2):181–185. doi: 10.1016/0014-5793(93)80269-z. [DOI] [PubMed] [Google Scholar]
  18. Gryglewski R. J., Palmer R. M., Moncada S. Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor. Nature. 1986 Apr 3;320(6061):454–456. doi: 10.1038/320454a0. [DOI] [PubMed] [Google Scholar]
  19. Haddad I. Y., Ischiropoulos H., Holm B. A., Beckman J. S., Baker J. R., Matalon S. Mechanisms of peroxynitrite-induced injury to pulmonary surfactants. Am J Physiol. 1993 Dec;265(6 Pt 1):L555–L564. doi: 10.1152/ajplung.1993.265.6.L555. [DOI] [PubMed] [Google Scholar]
  20. Halliwell B. Albumin--an important extracellular antioxidant? Biochem Pharmacol. 1988 Feb 15;37(4):569–571. doi: 10.1016/0006-2952(88)90126-8. [DOI] [PubMed] [Google Scholar]
  21. Halliwell B., Gutteridge J. M. Role of free radicals and catalytic metal ions in human disease: an overview. Methods Enzymol. 1990;186:1–85. doi: 10.1016/0076-6879(90)86093-b. [DOI] [PubMed] [Google Scholar]
  22. Halliwell B., Gutteridge J. M. The antioxidants of human extracellular fluids. Arch Biochem Biophys. 1990 Jul;280(1):1–8. doi: 10.1016/0003-9861(90)90510-6. [DOI] [PubMed] [Google Scholar]
  23. Halliwell B., Hu M. L., Louie S., Duvall T. R., Tarkington B. K., Motchnik P., Cross C. E. Interaction of nitrogen dioxide with human plasma. Antioxidant depletion and oxidative damage. FEBS Lett. 1992 Nov 16;313(1):62–66. doi: 10.1016/0014-5793(92)81185-o. [DOI] [PubMed] [Google Scholar]
  24. Huie R. E., Padmaja S. The reaction of no with superoxide. Free Radic Res Commun. 1993;18(4):195–199. doi: 10.3109/10715769309145868. [DOI] [PubMed] [Google Scholar]
  25. Ischiropoulos H., Zhu L., Beckman J. S. Peroxynitrite formation from macrophage-derived nitric oxide. Arch Biochem Biophys. 1992 Nov 1;298(2):446–451. doi: 10.1016/0003-9861(92)90433-w. [DOI] [PubMed] [Google Scholar]
  26. Ischiropoulos H., Zhu L., Chen J., Tsai M., Martin J. C., Smith C. D., Beckman J. S. Peroxynitrite-mediated tyrosine nitration catalyzed by superoxide dismutase. Arch Biochem Biophys. 1992 Nov 1;298(2):431–437. doi: 10.1016/0003-9861(92)90431-u. [DOI] [PubMed] [Google Scholar]
  27. Kagan V., Serbinova E., Packer L. Antioxidant effects of ubiquinones in microsomes and mitochondria are mediated by tocopherol recycling. Biochem Biophys Res Commun. 1990 Jun 29;169(3):851–857. doi: 10.1016/0006-291x(90)91971-t. [DOI] [PubMed] [Google Scholar]
  28. Katusic Z. S., Vanhoutte P. M. Superoxide anion is an endothelium-derived contracting factor. Am J Physiol. 1989 Jul;257(1 Pt 2):H33–H37. doi: 10.1152/ajpheart.1989.257.1.H33. [DOI] [PubMed] [Google Scholar]
  29. Kikugawa K., Kato T., Okamoto Y. Damage of amino acids and proteins induced by nitrogen dioxide, a free radical toxin, in air. Free Radic Biol Med. 1994 Mar;16(3):373–382. doi: 10.1016/0891-5849(94)90039-6. [DOI] [PubMed] [Google Scholar]
  30. Levine R. L., Garland D., Oliver C. N., Amici A., Climent I., Lenz A. G., Ahn B. W., Shaltiel S., Stadtman E. R. Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol. 1990;186:464–478. doi: 10.1016/0076-6879(90)86141-h. [DOI] [PubMed] [Google Scholar]
  31. Moncada S., Palmer R. M., Higgs E. A. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109–142. [PubMed] [Google Scholar]
  32. Moreno J. J., Pryor W. A. Inactivation of alpha 1-proteinase inhibitor by peroxynitrite. Chem Res Toxicol. 1992 May-Jun;5(3):425–431. doi: 10.1021/tx00027a017. [DOI] [PubMed] [Google Scholar]
  33. O'Neill C. A., van der Vliet A., Hu M. L., Kaur H., Cross C. E., Louie S., Halliwell B. Oxidation of biologic molecules by ozone: the effect of pH. J Lab Clin Med. 1993 Nov;122(5):497–505. [PubMed] [Google Scholar]
  34. Pryor W. A., Lightsey J. W. Mechanisms of nitrogen dioxide reactions: initiation of lipid peroxidation and the production of nitrous Acid. Science. 1981 Oct 23;214(4519):435–437. doi: 10.1126/science.214.4519.435. [DOI] [PubMed] [Google Scholar]
  35. Prütz W. A., Mönig H., Butler J., Land E. J. Reactions of nitrogen dioxide in aqueous model systems: oxidation of tyrosine units in peptides and proteins. Arch Biochem Biophys. 1985 Nov 15;243(1):125–134. doi: 10.1016/0003-9861(85)90780-5. [DOI] [PubMed] [Google Scholar]
  36. Radi R., Beckman J. S., Bush K. M., Freeman B. A. Peroxynitrite oxidation of sulfhydryls. The cytotoxic potential of superoxide and nitric oxide. J Biol Chem. 1991 Mar 5;266(7):4244–4250. [PubMed] [Google Scholar]
  37. Radi R., Beckman J. S., Bush K. M., Freeman B. A. Peroxynitrite-induced membrane lipid peroxidation: the cytotoxic potential of superoxide and nitric oxide. Arch Biochem Biophys. 1991 Aug 1;288(2):481–487. doi: 10.1016/0003-9861(91)90224-7. [DOI] [PubMed] [Google Scholar]
  38. Radi R., Cosgrove T. P., Beckman J. S., Freeman B. A. Peroxynitrite-induced luminol chemiluminescence. Biochem J. 1993 Feb 15;290(Pt 1):51–57. doi: 10.1042/bj2900051. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Stocker R., Bowry V. W., Frei B. Ubiquinol-10 protects human low density lipoprotein more efficiently against lipid peroxidation than does alpha-tocopherol. Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1646–1650. doi: 10.1073/pnas.88.5.1646. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Sun J. Z., Kaur H., Halliwell B., Li X. Y., Bolli R. Use of aromatic hydroxylation of phenylalanine to measure production of hydroxyl radicals after myocardial ischemia in vivo. Direct evidence for a pathogenetic role of the hydroxyl radical in myocardial stunning. Circ Res. 1993 Sep;73(3):534–549. doi: 10.1161/01.res.73.3.534. [DOI] [PubMed] [Google Scholar]
  41. Swain J. A., Darley-Usmar V., Gutteridge J. M. Peroxynitrite releases copper from caeruloplasmin: implications for atherosclerosis. FEBS Lett. 1994 Mar 28;342(1):49–52. doi: 10.1016/0014-5793(94)80582-2. [DOI] [PubMed] [Google Scholar]
  42. Wayner D. D., Burton G. W., Ingold K. U., Barclay L. R., Locke S. J. The relative contributions of vitamin E, urate, ascorbate and proteins to the total peroxyl radical-trapping antioxidant activity of human blood plasma. Biochim Biophys Acta. 1987 Jun 22;924(3):408–419. doi: 10.1016/0304-4165(87)90155-3. [DOI] [PubMed] [Google Scholar]
  43. White C. R., Brock T. A., Chang L. Y., Crapo J., Briscoe P., Ku D., Bradley W. A., Gianturco S. H., Gore J., Freeman B. A. Superoxide and peroxynitrite in atherosclerosis. Proc Natl Acad Sci U S A. 1994 Feb 1;91(3):1044–1048. doi: 10.1073/pnas.91.3.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Yamamoto Y., Brodsky M. H., Baker J. C., Ames B. N. Detection and characterization of lipid hydroperoxides at picomole levels by high-performance liquid chromatography. Anal Biochem. 1987 Jan;160(1):7–13. doi: 10.1016/0003-2697(87)90606-3. [DOI] [PubMed] [Google Scholar]
  45. Zhu L., Gunn C., Beckman J. S. Bactericidal activity of peroxynitrite. Arch Biochem Biophys. 1992 Nov 1;298(2):452–457. doi: 10.1016/0003-9861(92)90434-x. [DOI] [PubMed] [Google Scholar]
  46. van der Vliet A., O'Neill C. A., Halliwell B., Cross C. E., Kaur H. Aromatic hydroxylation and nitration of phenylalanine and tyrosine by peroxynitrite. Evidence for hydroxyl radical production from peroxynitrite. FEBS Lett. 1994 Feb 14;339(1-2):89–92. doi: 10.1016/0014-5793(94)80391-9. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES