Published online before print June 27, 2002, doi: 10.1161/01.ATV.0000027524.86752.02
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2002 American Heart Association, Inc.
Vascular Biology |
Peroxidase Properties of Extracellular Superoxide Dismutase
Role of Uric Acid in Modulating In Vivo Activity
From the Division of Cardiology, Department of Medicine (H.U.H., S.D., L.M., A.D.N., D.G.H., T.F.), and the Department of Gynecology and Obstetrics (N.S., S.P.), Emory University School of Medicine, and the Atlanta Veterans Administration Hospital (L.M., D.G.H., T.F.), Atlanta, Ga.
Correspondence to Tohru Fukai, MD, PhD, Division of Cardiology, Emory University School of Medicine, 1639 Pierce Dr, WMB 319, Atlanta, GA 30322. E-mail tfukai{at}emory.edu
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.
Key Words: superoxide dismutase • peroxidase activity • uric acid • hydrogen peroxide • atherosclerosis
This article has been cited by other articles:
 |
|
 |
|
  J. F. Baker, H. R. Schumacher, and E. Krishnan Serum Uric Acid Level and Risk for Peripheral Arterial Disease: Analysis of Data From the Multiple Risk Factor Intervention Trial Angiology, September 1, 2007; 58(4): 450 - 457. [Abstract] [PDF]
|
|
|
|
 |
|
 D. Patschan, S. Patschan, G. G. Gobe, S. Chintala, and M. S. Goligorsky Uric Acid Heralds Ischemic Tissue Injury to Mobilize Endothelial Progenitor Cells J. Am. Soc. Nephrol., May 1, 2007; 18(5): 1516 - 1524. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Fukai Extracellular SOD Inactivation in High-Volume Hypertension: Role of Hydrogen Peroxide Arterioscler. Thromb. Vasc. Biol., March 1, 2007; 27(3): 442 - 444. [Full Text] [PDF]
|
|
|
|
|
|
O. Jung, S. L. Marklund, N. Xia, R. Busse, and R. P. Brandes Inactivation of Extracellular Superoxide Dismutase Contributes to the Development of High-Volume Hypertension Arterioscler. Thromb. Vasc. Biol., March 1, 2007; 27(3): 470 - 477. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Ejaz, W. Mu, D.-H. Kang, C. Roncal, Y. Y. Sautin, G. Henderson, I. Tabah-Fisch, B. Keller, T. M. Beaver, T. Nakagawa, et al. Could Uric Acid Have a Role in Acute Renal Failure? Clin. J. Am. Soc. Nephrol., January 1, 2007; 2(1): 16 - 21. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Gongora, Z. Qin, K. Laude, H. W. Kim, L. McCann, J. R. Folz, S. Dikalov, T. Fukai, and D. G. Harrison Role of Extracellular Superoxide Dismutase in Hypertension Hypertension, September 1, 2006; 48(3): 473 - 481. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. D. Heistad Oxidative Stress and Vascular Disease: 2005 Duff Lecture Arterioscler. Thromb. Vasc. Biol., April 1, 2006; 26(4): 689 - 695. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Jeney, S. Itoh, M. Wendt, Q. Gradek, M. Ushio-Fukai, D. G. Harrison, and T. Fukai Role of Antioxidant-1 in Extracellular Superoxide Dismutase Function and Expression Circ. Res., April 15, 2005; 96(7): 723 - 729. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. P. Wilkinson and A. Grove HucR, a Novel Uric Acid-responsive Member of the MarR Family of Transcriptional Regulators from Deinococcus radiodurans J. Biol. Chem., December 3, 2004; 279(49): 51442 - 51450. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ohtsubo, I. I. Rovira, M. F. Starost, C. Liu, and T. Finkel Xanthine Oxidoreductase Is an Endogenous Regulator of Cyclooxygenase-2 Circ. Res., November 26, 2004; 95(11): 1118 - 1124. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Stocker and J. F. Keaney Jr. Role of Oxidative Modifications in Atherosclerosis Physiol Rev, October 1, 2004; 84(4): 1381 - 1478. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Seo, T. Wang, H. Dressman, E. E. Herderick, E. S. Iversen, C. Dong, K. Vata, C. A. Milano, F. Rigat, J. Pittman, et al. Gene Expression Phenotypes of Atherosclerosis Arterioscler. Thromb. Vasc. Biol., October 1, 2004; 24(10): 1922 - 1927. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. C. Schulze, J. Yoshioka, T. Takahashi, Z. He, G. L. King, and R. T. Lee Hyperglycemia Promotes Oxidative Stress through Inhibition of Thioredoxin Function by Thioredoxin-interacting Protein J. Biol. Chem., July 16, 2004; 279(29): 30369 - 30374. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. B. Suliman, M. Ali, and C. A. Piantadosi Superoxide dismutase-3 promotes full expression of the EPO response to hypoxia Blood, July 1, 2004; 104(1): 43 - 50. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-P. Hsu, M.-F. Pai, Y.-S. Peng, C.-K. Chiang, T.-I Ho, and K.-Y. Hung Serum uric acid levels show a 'J-shaped' association with all-cause mortality in haemodialysis patients Nephrol. Dial. Transplant., February 1, 2004; 19(2): 457 - 462. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. F. Leite, A. Danilovic, P. Moriel, K. Dantas, S. Marklund, A. P. V. Dantas, and F. R.M. Laurindo Sustained Decrease in Superoxide Dismutase Activity Underlies Constrictive Remodeling After Balloon Injury in Rabbits Arterioscler. Thromb. Vasc. Biol., December 1, 2003; 23(12): 2197 - 2202. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Kanellis and R. J. Johnson Editorial Comment--Elevated Uric Acid and Ischemic Stroke: Accumulating Evidence That It Is Injurious and Not Neuroprotective Stroke, August 1, 2003; 34(8): 1956 - 1957. [Full Text] [PDF]
|
|
|
|
|
|
H. Zhang, C. Andrekopoulos, J. Joseph, K. Chandran, H. Karoui, J. P. Crow, and B. Kalyanaraman Bicarbonate-dependent Peroxidase Activity of Human Cu,Zn-Superoxide Dismutase Induces Covalent Aggregation of Protein: INTERMEDIACY OF TRYPTOPHAN-DERIVED OXIDATION PRODUCTS J. Biol. Chem., June 20, 2003; 278(26): 24078 - 24089. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Johnson, D.-H. Kang, D. Feig, S. Kivlighn, J. Kanellis, S. Watanabe, K. R. Tuttle, B. Rodriguez-Iturbe, J. Herrera-Acosta, and M. Mazzali Is There a Pathogenetic Role for Uric Acid in Hypertension and Cardiovascular and Renal Disease? Hypertension, June 1, 2003; 41(6): 1183 - 1190. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Hare and R. J. Johnson Uric Acid Predicts Clinical Outcomes in Heart Failure: Insights Regarding the Role of Xanthine Oxidase and Uric Acid in Disease Pathophysiology Circulation, April 22, 2003; 107(15): 1951 - 1953. [Full Text] [PDF]
|
|
|
|
|
|
U. Landmesser and H. Drexler Toward Understanding of Extracellular Superoxide Dismutase Regulation in Atherosclerosis: A Novel Role of Uric Acid? Arterioscler. Thromb. Vasc. Biol., September 1, 2002; 22(9): 1367 - 1368. [Full Text] [PDF]
|
|