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 language | English (US) |
|---|---|
| Pages (from-to) | 1402-1408 |
| Number of pages | 7 |
| Journal | Arteriosclerosis, thrombosis, and vascular biology |
| Volume | 22 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 1 2002 |
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Keywords
- Atherosclerosis
- Hydrogen peroxide
- Peroxidase activity
- Superoxide dismutase
- Uric acid
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
Cite this
Peroxidase properties of extracellular superoxide dismutase role of uric acid in modulating in vivo activity. / Hink, H. Ulrich; Santanam, Nalini; Dikalov, Sergey; McCann, Louise; Nguyen, Andrew D.; Parthasarathy, Sampath; Harrison, David G.; Fukai, Tohru.
In: Arteriosclerosis, thrombosis, and vascular biology, Vol. 22, No. 9, 01.09.2002, p. 1402-1408.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Peroxidase properties of extracellular superoxide dismutase role of uric acid in modulating in vivo activity
AU - Hink, H. Ulrich
AU - Santanam, Nalini
AU - Dikalov, Sergey
AU - McCann, Louise
AU - Nguyen, Andrew D.
AU - Parthasarathy, Sampath
AU - Harrison, David G.
AU - Fukai, Tohru
PY - 2002/9/1
Y1 - 2002/9/1
N2 - 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.
AB - 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.
KW - Atherosclerosis
KW - Hydrogen peroxide
KW - Peroxidase activity
KW - Superoxide dismutase
KW - Uric acid
UR - http://www.scopus.com/inward/record.url?scp=0036736747&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036736747&partnerID=8YFLogxK
U2 - 10.1161/01.ATV.0000027524.86752.02
DO - 10.1161/01.ATV.0000027524.86752.02
M3 - Article
C2 - 12231557
AN - SCOPUS:0036736747
VL - 22
SP - 1402
EP - 1408
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
SN - 1079-5642
IS - 9
ER -