title: Peroxidase properties of extracellular superoxide dismutase: role of uric acid in modulating in vivo activity.
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.
  
  
  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 approximately 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.
authors.affiliation: Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Ga 30322, USA.
authors.forename: H Ulrich
authors.initials: HU
authors.lastname: Hink
authors.forename: Nalini
authors.initials: N
authors.lastname: Santanam
authors.forename: Sergey
authors.initials: S
authors.lastname: Dikalov
authors.forename: Louise
authors.initials: L
authors.lastname: McCann
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Nguyen
authors.forename: Sampath
authors.initials: S
authors.lastname: Parthasarathy
authors.forename: David G
authors.initials: DG
authors.lastname: Harrison
authors.forename: Tohru
authors.initials: T
authors.lastname: Fukai
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000502:physiology; D001161:Arteriosclerosis / Q000201:enzymology; D001639:Bicarbonates / Q000378:metabolism; D005110:Extracellular Space / Q000201:enzymology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009195:Peroxidase / Q000378:metabolism*; D010843:Pichia / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D019097:Spin Trapping / Q000379:methods; D013379:Substrate Specificity; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D014162:Transfection; D014527:Uric Acid / Q000097:blood / Q000378:metabolism*
chemical_list: D001057:Apolipoproteins E; D001639:Bicarbonates; D011994:Recombinant Proteins; D014527:Uric Acid; D006861:Hydrogen Peroxide; D009195:Peroxidase; C000606291:Sod1 protein, mouse; C499090:Sod3 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1