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Gene Review

Sod3  -  superoxide dismutase 3, extracellular

Rattus norvegicus

Synonyms: EC-SOD, Sod-3, Superoxide dismutase B
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Disease relevance of Sod3

  • Purification and sequence of rat extracellular superoxide dismutase B secreted by C6 glioma [1].
  • In summary, efficient overexpression of ECSOD, but not MnSOD in vivo, results in improved endothelial function in a rat model of hypertension and has important implications for the development of endothelial-based vascular gene therapy [2].
  • Reactive oxygen species (ROS) have been implicated in the pathogenesis of rheumatoid arthritis (RA), while antioxidant enzymes, such as extracellular superoxide dismutase (EC-SOD) and catalase, block radical-induced events [3].
  • Three days after gene transfer of adenovirus expressing human ECSOD (AdECSOD), the response to ACh was not affected in young rats but was improved in old rats [4].

Psychiatry related information on Sod3

  • Gene-transfer of EC-SOD reduces superoxide formation and restores age-associated erectile function and may represent a novel therapeutic target for the treatment of erectile dysfunction [5].

High impact information on Sod3

  • While EC-SOD from most mammals is tetrameric and has a high affinity for heparin and heparan sulfate, rat EC-SOD has a low affinity for heparin, does not bind to heparan sulfate in vivo, and is apparently dimeric [6].
  • To examine the molecular basis of the deviant physical properties of rat EC-SOD, the cDNAs of the rat and mouse EC-SODs were isolated and the deduced amino acid sequences were compared with that of human EC-SOD [6].
  • Extracellular superoxide dismutase (EC-SOD) is a secreted Cu and Zn-containing glycoprotein [6].
  • Trientine caused the Cu balance to become negative in diabetic subjects through elevated urinary Cu losses and suppressed elevated EC-SOD [7].
  • Extracellular superoxide dismutase (EC-SOD) is an antioxidant enzyme that attenuates brain and lung injury from oxidative stress [8].

Chemical compound and disease context of Sod3

  • Adenoviruses containing ECSOD (AdECSOD), ECSOD with deletion of its heparin-binding domain (AdECSOD-HBD), or a control virus (AdLacZ) were injected intravenously into rats [9].

Biological context of Sod3

  • Although rat EC-SOD has a high sequence homology with the catalytic center and the polybasic heparin-binding site near the COOH terminus of human EC-SOD C, its NH2-terminal sequence and the sequences flanking the heparin-binding site differ substantially [1].
  • These results indicate that furin-dependent processing of EC-SOD is important for determining the tissue distribution and half-life of EC-SOD [8].
  • This wide variation in EC-SOD content suggests that the susceptibility to pathologies induced by superoxide radicals in the vascular wall interstitium should vary widely among species [10].
  • Upregulation of HO-1 expression by intermittent administration of cobalt protoporphyrin, an inducer of HO-1 protein and activity, resulted in a robust increase in EC-SOD but no significant change in Cu-Zn-SOD [11].
  • Similarly, augmented iNOS expression, apoptosis and collagen content in the vascular wall were also reduced by EC-SOD treatment [12].

Anatomical context of Sod3

  • Neutrophils and macrophages invading the lung showed an intensive staining for the EC-SOD protein concomitantly with a decrease of the enzyme in the plasma [13].
  • In control rats, EC-SOD mRNA was synthesized in macrophages and in cells of the arterial vessel walls and the alveolar septa [13].
  • Arterial smooth muscle cells were found to secrete large amounts of EC-SOD and likely are the principal source of the enzyme in the vascular wall [10].
  • The presented data demonstrated that in lung tissue the EC-SOD enzyme may have a protective function for activated macrophages, neutrophils, and lympoid tissue-associated epithelial cells [13].
  • The EC-SOD concentration in the human arterial wall extracellular space is high enough to efficiently suppress the putative pathological effects of the superoxide radical, such as oxidation of LDL and reaction with nitric oxide to form the deleterious peroxynitrite [10].

Associations of Sod3 with chemical compounds

  • Exposure to hyperoxia did not affect the distribution of EC-SOD mRNA and protein [13].
  • Immunohistochemistry (IHC) and in situ hybridization (ISH) was used to localize extracellular superoxide dismutase (EC-SOD) and its mRNA in rat lung before and after a lipopolysaccharide (LPS)- and hyperoxia-induced inflammation [13].
  • The potency to enhance EC-SOD expression is correlated with the ability of the cAMP analogue to induce cAMP-dependent differentiation in C6 [14].
  • Example of interference were stimulation of xanthine oxidase activity, color formation without xanthine oxidase, color formation despite excess Cu-Zn SOD addition, and absorbance changes with cyanide inhibition of EC SOD that were above or below blank values [15].
  • Analysis of rat plasma fractionated with Sephadex G-150 showed that each assay (three xanthine oxidase based assays plus a modified pyrogallol assay) detected apparent SOD activity almost entirely at the same molecular weight as rat lung EC SOD [15].

Regulatory relationships of Sod3


Other interactions of Sod3

  • Vascular EC-SOD and plasma catalase activities were significantly reduced in diabetic compared with nondiabetic rats (P < 0.05) [11].
  • Administration of tin mesoporphyrin, an inhibitor of HO-1 activity, decreased EC-SOD protein [11].
  • Treatment of the cells with heparin alone decreased HB-EGF expression by 20%, whereas EC-SOD alone and a co-incubation with EC-SOD and heparin suppressed the induction by 60 and 70%, respectively [16].
  • The observation that EC-SOD and iNOS are temporally coregulated after cytokine exposure suggests the possibility of a critical mechanism by which cells might protect .NO and avoid the formation of OONO- during inflammation [17].
  • METHODS AND RESULTS: We assessed the expression of EC-SOD and GRP78 mRNA in cultured rat VSMCs by Northern blot analysis [18].

Analytical, diagnostic and therapeutic context of Sod3


  1. Purification and sequence of rat extracellular superoxide dismutase B secreted by C6 glioma. Willems, J., Zwijsen, A., Slegers, H., Nicolaï, S., Bettadapura, J., Raymackers, J., Scarcez, T. J. Biol. Chem. (1993) [Pubmed]
  2. Adenovirus-mediated overexpression of extracellular superoxide dismutase improves endothelial dysfunction in a rat model of hypertension. Fennell, J.P., Brosnan, M.J., Frater, A.J., Hamilton, C.A., Alexander, M.Y., Nicklin, S.A., Heistad, D.D., Baker, A.H., Dominiczak, A.F. Gene Ther. (2002) [Pubmed]
  3. Amelioration of antigen-induced arthritis in rats by transfer of extracellular superoxide dismutase and catalase genes. Dai, L., Claxson, A., Marklund, S.L., Feakins, R., Yousaf, N., Chernajovsky, Y., Winyard, P.G. Gene Ther. (2003) [Pubmed]
  4. Gene transfer of extracellular superoxide dismutase protects against vascular dysfunction with aging. Brown, K.A., Chu, Y., Lund, D.D., Heistad, D.D., Faraci, F.M. Am. J. Physiol. Heart Circ. Physiol. (2006) [Pubmed]
  5. Gene transfer of extracellular SOD to the penis reduces O2-* and improves erectile function in aged rats. Bivalacqua, T.J., Armstrong, J.S., Biggerstaff, J., Abdel-Mageed, A.B., Kadowitz, P.J., Hellstrom, W.J., Champion, H.C. Am. J. Physiol. Heart Circ. Physiol. (2003) [Pubmed]
  6. The rat extracellular superoxide dismutase dimer is converted to a tetramer by the exchange of a single amino acid. Carlsson, L.M., Marklund, S.L., Edlund, T. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  7. Demonstration of a hyperglycemia-driven pathogenic abnormality of copper homeostasis in diabetes and its reversibility by selective chelation: quantitative comparisons between the biology of copper and eight other nutritionally essential elements in normal and diabetic individuals. Cooper, G.J., Chan, Y.K., Dissanayake, A.M., Leahy, F.E., Keogh, G.F., Frampton, C.M., Gamble, G.D., Brunton, D.H., Baker, J.R., Poppitt, S.D. Diabetes (2005) [Pubmed]
  8. Furin proteolytically processes the heparin-binding region of extracellular superoxide dismutase. Bowler, R.P., Nicks, M., Olsen, D.A., Thøgersen, I.B., Valnickova, Z., Højrup, P., Franzusoff, A., Enghild, J.J., Crapo, J.D. J. Biol. Chem. (2002) [Pubmed]
  9. Gene transfer of extracellular superoxide dismutase improves relaxation of aorta after treatment with endotoxin. Lund, D.D., Gunnett, C.A., Chu, Y., Brooks, R.M., Faraci, F.M., Heistad, D.D. Am. J. Physiol. Heart Circ. Physiol. (2004) [Pubmed]
  10. The interstitium of the human arterial wall contains very large amounts of extracellular superoxide dismutase. Strålin, P., Karlsson, K., Johansson, B.O., Marklund, S.L. Arterioscler. Thromb. Vasc. Biol. (1995) [Pubmed]
  11. Antioxidant mechanism of heme oxygenase-1 involves an increase in superoxide dismutase and catalase in experimental diabetes. Turkseven, S., Kruger, A., Mingone, C.J., Kaminski, P., Inaba, M., Rodella, L.F., Ikehara, S., Wolin, M.S., Abraham, N.G. Am. J. Physiol. Heart Circ. Physiol. (2005) [Pubmed]
  12. Extracellular superoxide dismutase overexpression reduces cuff-induced arterial neointimal formation. Ozumi, K., Tasaki, H., Takatsu, H., Nakata, S., Morishita, T., Koide, S., Yamashita, K., Tsutsui, M., Okazaki, M., Sasaguri, Y., Adachi, T., Nakashima, Y. Atherosclerosis (2005) [Pubmed]
  13. Localization of extracellular superoxide dismutase in rat lung: neutrophils and macrophages as carriers of the enzyme. Loenders, B., Van Mechelen, E., Nicolaï, S., Buyssens, N., Van Osselaer, N., Jorens, P.G., Willems, J., Herman, A.G., Slegers, H. Free Radic. Biol. Med. (1998) [Pubmed]
  14. Cyclic AMP-induced differentiation increases the synthesis of extracellular superoxide dismutase in rat C6 glioma. Nicolaï, S., Willems, J., Zwijsen, A., Van Mechelen, E., Slegers, H. Free Radic. Biol. Med. (1996) [Pubmed]
  15. Comparison of four indirect methods for fluid superoxide dismutase activities. DiSilvestro, R.A., David, C., David, E.A. Free Radic. Biol. Med. (1990) [Pubmed]
  16. Inhibition of gene expression of heparin-binding epidermal growth factor-like growth factor by extracellular superoxide dismutase in rat aortic smooth muscle cells. Nishimura, M., Ookawara, T., Eguchi, H., Fujiwara, N., Yoshihara, D., Yasuda, J., Mimura, O., Suzuki, K. Free Radic. Res. (2006) [Pubmed]
  17. Extracellular superoxide dismutase is upregulated with inducible nitric oxide synthase after NF-kappa B activation. Brady, T.C., Chang, L.Y., Day, B.J., Crapo, J.D. Am. J. Physiol. (1997) [Pubmed]
  18. Taurine prevents the decrease in expression and secretion of extracellular superoxide dismutase induced by homocysteine: amelioration of homocysteine-induced endoplasmic reticulum stress by taurine. Nonaka, H., Tsujino, T., Watari, Y., Emoto, N., Yokoyama, M. Circulation (2001) [Pubmed]
  19. Discordant extracellular superoxide dismutase expression and activity in neonatal hyperoxic lung. Mamo, L.B., Suliman, H.B., Giles, B.L., Auten, R.L., Piantadosi, C.A., Nozik-Grayck, E. Am. J. Respir. Crit. Care Med. (2004) [Pubmed]
  20. Endothelium bound extracellular superoxide dismutase type C reduces damage in reperfused ischaemic rat hearts. Sjöquist, P.O., Marklund, S.L. Cardiovasc. Res. (1992) [Pubmed]
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