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

Hink HU, Santanam N, Dikalov S, McCann L, Nguyen AD, Parthasarathy S, Harrison DG, Fukai T
Arterioscler Thromb Vasc Biol. 2002 22 (9): 1402-8

PMID: 12231557

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 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.

MeSH Terms (18)

Animals Apolipoproteins E Arteriosclerosis Bicarbonates Extracellular Space Hydrogen Peroxide Mice Mice, Inbred C57BL Mice, Mutant Strains Peroxidase Pichia Recombinant Proteins Spin Trapping Substrate Specificity Superoxide Dismutase Superoxide Dismutase-1 Transfection Uric Acid

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