Peroxidase properties of extracellular superoxide dismutase role of uric acid in modulating in vivo activity

H. Ulrich Hink, Nalini Santanam, Sergey Dikalov, Louise McCann, Andrew D. Nguyen, Sampath Parthasarathy, David G. Harrison, Tohru Fukai

Research output: Contribution to journalArticle

152 Scopus citations

Abstract

Objective - The cytosolic form of Cu/Zn-containing superoxide dismutase (SOD1) has peroxidase activity, with H2O2 used as a substrate to oxidize other molecules. We examined peroxidase properties of the extracellular form of SOD (SOD3), a major isoform of SOD in the vessel wall, by using recombinant SOD3 and an in vivo model of atherosclerosis. Methods and Results - In the presence of HCO3-, SOD3 reacted with H2O2 to produce a hydroxyl radical adduct of the spin trap 5-diethoxyphosphoryl-5methyl-1-pyrroline N-oxide (DEMPO). SOD1 and SOD3 were inactivated by H2O2 in a dose- and time-dependent fashion, and this was prevented by physiological levels of uric acid. To examine the in vivo role of uric acid on SOD1 and SOD3, control and apolipoprotein E-deficient (ApoE-/-) mice were treated with oxonic acid, which inhibits urate metabolism. This treatment increased plasma levels of uric acid in control and ApoE-/- mice by ≈3-fold. Although increasing uric acid levels did not alter aortic SOD1 and SOD3 protein expression, aortic SOD1 and SOD3 activities were increased by 2- to 3-fold in aortas from ApoE-/- mice but not in aortas from control mice. Conclusions - These studies show that SOD1 and SOD3 are partially inactivated in atherosclerotic vessels of ApoE-/- mice and that levels of uric acid commonly encountered in vivo may regulate vascular redox state by preserving the activity of these enzymes.

Original languageEnglish (US)
Pages (from-to)1402-1408
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Volume22
Issue number9
DOIs
StatePublished - Sep 2002
Externally publishedYes

Keywords

  • Atherosclerosis
  • Hydrogen peroxide
  • Peroxidase activity
  • Superoxide dismutase
  • Uric acid

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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