Hydrogen peroxide is the major oxidant product of xanthine oxidase

Eric E. Kelley, Nicholas K H Khoo, Nicholas J. Hundley, Umair Z. Malik, Bruce A. Freeman, Margaret M. Tarpey

Research output: Contribution to journalArticlepeer-review

240 Scopus citations

Abstract

Xanthine oxidase (XO) is a critical source of reactive oxygen species (ROS) in inflammatory disease. Focus, however, has centered almost exclusively on XO-derived superoxide (O2•-), whereas direct H2O2 production from XO has been less well investigated. Therefore, we examined the relative quantities of O2•- and H2O2 produced by XO under a range (1-21%) of O2 tensions. At O2 concentrations between 10 and 21%, H2O2 accounted for ∼75% of ROS production. As O2 concentrations were lowered, there was a concentration-dependent increase in H2O2 formation, accounting for 90% of ROS production at 1% O2. Alterations in pH between 5.5 and 7.4 did not affect the relative proportions of H2O2 and O2•- formation. Immobilization of XO, by binding to heparin-Sepharose, further enhanced relative H2O2 production by ∼30%, under both normoxic and hypoxic conditions. Furthermore, XO bound to glycosaminoglycans on the apical surface of bovine aortic endothelial cells demonstrated a similar ROS production profile. These data establish H2O2 as the dominant (70-95%) reactive product produced by XO under clinically relevant conditions and emphasize the importance of H2O2 as a critical factor when examining the contributory roles of XO-catalyzed ROS in inflammatory processes as well as cellular signaling.

Original languageEnglish (US)
Pages (from-to)493-498
Number of pages6
JournalFree Radical Biology and Medicine
Volume48
Issue number4
DOIs
StatePublished - Feb 15 2010

Keywords

  • Free radicals
  • Hydrogen peroxide
  • Hypoxia
  • Oxygen
  • Reactive oxygen species
  • Superoxide
  • Xanthine oxidase

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