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Gene Review

SOD2  -  superoxide dismutase 2, mitochondrial

Homo sapiens

Synonyms: IPOB, MNSOD, MVCD6
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Disease relevance of SOD2


Psychiatry related information on SOD2

  • Manganese superoxide dismutase (MnSOD: Ala-9Val) gene polymorphism and mood disorders: A preliminary study [6].
  • The Mn-SOD concentration was significantly (P<0.05, U-test) reduced in patients suffering from Alzheimer's disease if compared to non-demented controls [7].

High impact information on SOD2

  • Yeast, lacking either Cu, ZnSOD or MnSOD, are oxygen intolerant, and the double mutant was hypermutable and defective in sporulation and exhibited requirements for methionine and lysine [8].
  • We report here that after refitting and further refinement of the previous 2 A structure of SOD2, analysis of the new model and its calculated molecular surface shows an extensive surface topography of sequence-conserved residues stabilized by underlying tight packing and H-bonding [9].
  • Manganese superoxide dismutase 2 (SOD2) is a critical component of the mitochondrial pathway for detoxification of O2(-), and targeted disruption of this locus leads to embryonic or neonatal lethality in mice [1].
  • Loss of SOD2 in erythroid progenitor cells results in enhanced protein oxidative damage, altered membrane deformation, and reduced survival of red cells [1].
  • However, the observed superoxide production rates are modulated by the variant induction of MnSOD which decreases the rates, sometimes below those seen in control fibroblast mitochondria [10].

Chemical compound and disease context of SOD2


Biological context of SOD2

  • We have created P1 artificial chromosome transgenic mice expressing the human mitochondrial superoxide dismutase 2 (SOD2) and thus generated mice with a physiologically controlled augmentation of SOD2 expression leading to increased SOD2 enzyme activities and lowered superoxide levels [15].
  • Our findings suggest a possible association between decreased SOD2 activity and malignant phenotype [16].
  • Manganese-dependent superoxide dismutase 2 (SOD2) in the mitochondria plays a key role in protection against oxidative stress [17].
  • These findings raise the hypothesis that p53 and SOD2 genes are mutually regulated leading to the modulation of various cellular processes including apoptosis [18].
  • We demonstrate here that p53 is able to repress SOD2 gene expression and that this repression takes place at promoter level [18].

Anatomical context of SOD2


Associations of SOD2 with chemical compounds

  • Here we demonstrate that release of mROS activates a signal relay pathway in which the serine/threonine protein kinase D (PKD) activates the NF-kappaB transcription factor, leading to induction of SOD2 [20].
  • In cell-free extracts, thiols quickly eliminated the SOD2 activity [16].
  • Here we probed the pathway by which SOD2 acquires its manganese catalytic cofactor [17].
  • Interestingly, cytogenetics have previously indicated that deletions of the long arm of chromosome 6, which carry the gene for SOD2, were frequently observed in parental but not in FUra-adapted cells [21].
  • Although native SOD2 has no affinity for heparin, SOD2/3 binds to a heparin-agarose column [5].

Physical interactions of SOD2

  • We constructed a fusion gene encoding a chimeric SOD consisting of the mature human mitochondrial SOD2 plus the COOH-terminal 26-amino acid heparin-binding "tail" from SOD3 [5].

Regulatory relationships of SOD2

  • Unlike iNOS-negative tumors, all iNOS-positive tumors coexpressed SOD1 or SOD2 [22].
  • Cu/Zn-SOD in the cytosol and Mn-SOD in mitochondria each are capable of protecting HepG2 cells expressing CYP2E1 against cytotoxicity induced by pro-oxidants [23].
  • Interestingly, Ad-p53 was able to inhibit TNF-induced MnSOD mRNA expression in MCF7/Adr cells, which might contribute to the sensitization of cells to the cytotoxic action of TNF [24].
  • A specific antibody against IL-6 almost completely inhibited the induction of Mn-SOD [25].
  • These results are consistent with multiple levels of control for SOD-1 expression and with a strong transcriptional influence on SOD-2 expression [26].

Other interactions of SOD2

  • Identification of nucleophosmin as an NF-kappaB co-activator for the induction of the human SOD2 gene [27].
  • Total SOD activity was fairly constant, whereas the ratio SOD2/SOD1 was much lower in TF than in NF [28].
  • The higher SOD2 and lower G6PD activity observed in FUra-resistant cell in comparison with parental cells at all times after sub-culture could be characteristic both of differentiative and of differentiated cells [21].
  • We were unable to replicate the previously observed association with SOD2 Val-9Ala and also found no association between breast cancer and GPX1 Pro198Leu [4].
  • No association between SOD2 or NQO1 genotypes and risk of bladder cancer [29].

Analytical, diagnostic and therapeutic context of SOD2

  • The amounts of SOD1, SOD2 and CAT immunoreactive proteins, estimated by Western blotting, appeared to be correlated to their respective enzymatic activities [21].
  • The data from ELISA and WB analysis showed that there were increased expressions of SOD1 and SOD3 protein in polyp tissues compared with the control tissues, but there was no difference in the expression of SOD2 protein between the two groups [30].
  • Single IV injections of SOD2/3 have protected experimental animals against a variety of models involving inflammation or ischemia/reperfusion [31].
  • DESIGN AND METHODS: Data from two population-based, case-control studies of lymphoma in the UK (700 cases and 915 controls) and USA (1593 cases and 2517 controls) were pooled to analyze polymorphisms in genes involved in the oxidative stress response (SOD2 Val16Ala, CAT C-262T and GPX1 Pro197Leu) [32].
  • Polymorphisms in genes related to oxidative stress (MPO, MnSOD, CAT) and survival after treatment for breast cancer [33].


  1. Absence of mitochondrial superoxide dismutase results in a murine hemolytic anemia responsive to therapy with a catalytic antioxidant. Friedman, J.S., Rebel, V.I., Derby, R., Bell, K., Huang, T.T., Kuypers, F.A., Epstein, C.J., Burakoff, S.J. J. Exp. Med. (2001) [Pubmed]
  2. Beta-adrenergic receptor stimulation and adenoviral overexpression of superoxide dismutase prevent the hypoxia-mediated decrease in Na,K-ATPase and alveolar fluid reabsorption. Litvan, J., Briva, A., Wilson, M.S., Budinger, G.R., Sznajder, J.I., Ridge, K.M. J. Biol. Chem. (2006) [Pubmed]
  3. Early superoxide dismutase alterations during SV40-transformation of human fibroblasts. Bravard, A., Hoffschir, F., Sabatier, L., Ricoul, M., Pinton, A., Cassingena, R., Estrade, S., Luccioni, C., Dutrillaux, B. Int. J. Cancer (1992) [Pubmed]
  4. Genetic variants of GPX1 and SOD2 and breast cancer risk at the Ontario site of the Breast Cancer Family Registry. Knight, J.A., Onay, U.V., Wells, S., Li, H., Shi, E.J., Andrulis, I.L., Ozcelik, H. Cancer Epidemiol. Biomarkers Prev. (2004) [Pubmed]
  5. Synthesis and anti-inflammatory activity of a chimeric recombinant superoxide dismutase: SOD2/3. Gao, B., Flores, S.C., Leff, J.A., Bose, S.K., McCord, J.M. Am. J. Physiol. Lung Cell Mol. Physiol. (2003) [Pubmed]
  6. Manganese superoxide dismutase (MnSOD: Ala-9Val) gene polymorphism and mood disorders: A preliminary study. Pae, C.U., Yoon, S.J., Patkar, A., Kim, J.J., Jun, T.Y., Lee, C., Paik, I.H. Prog. Neuropsychopharmacol. Biol. Psychiatry (2006) [Pubmed]
  7. Oxidative-stress associated parameters (lactoferrin, superoxide dismutases) in serum of patients with Alzheimer's disease. Thome, J., Gsell, W., Rösler, M., Kornhuber, J., Frölich, L., Hashimoto, E., Zielke, B., Wiesbeck, G.A., Riederer, P. Life Sci. (1997) [Pubmed]
  8. Superoxide radical and superoxide dismutases. Fridovich, I. Annu. Rev. Biochem. (1995) [Pubmed]
  9. Structure and mechanism of copper, zinc superoxide dismutase. Tainer, J.A., Getzoff, E.D., Richardson, J.S., Richardson, D.C. Nature (1983) [Pubmed]
  10. Mitochondrial complex I deficiency leads to increased production of superoxide radicals and induction of superoxide dismutase. Pitkanen, S., Robinson, B.H. J. Clin. Invest. (1996) [Pubmed]
  11. MnSOD inhibits proline oxidase-induced apoptosis in colorectal cancer cells. Liu, Y., Borchert, G.L., Donald, S.P., Surazynski, A., Hu, C.A., Weydert, C.J., Oberley, L.W., Phang, J.M. Carcinogenesis (2005) [Pubmed]
  12. HIV-1 Tat potentiates TNF-induced NF-kappa B activation and cytotoxicity by altering the cellular redox state. Westendorp, M.O., Shatrov, V.A., Schulze-Osthoff, K., Frank, R., Kraft, M., Los, M., Krammer, P.H., Dröge, W., Lehmann, V. EMBO J. (1995) [Pubmed]
  13. Interaction between polymorphisms of the dopamine D3 receptor and manganese superoxide dismutase genes in susceptibility to tardive dyskinesia. Zhang, Z.J., Zhang, X.B., Hou, G., Yao, H., Reynolds, G.P. Psychiatr. Genet. (2003) [Pubmed]
  14. Cytokine action and oxidative stress response in differentiated neuroblastoma SH-SY5Y cells. Kania, J., Barańska, A., Guzdek, A. Acta Biochim. Pol. (2003) [Pubmed]
  15. SOD2 overexpression: enhanced mitochondrial tolerance but absence of effect on UCP activity. Silva, J.P., Shabalina, I.G., Dufour, E., Petrovic, N., Backlund, E.C., Hultenby, K., Wibom, R., Nedergaard, J., Cannon, B., Larsson, N.G. EMBO J. (2005) [Pubmed]
  16. Paradoxical effects of thiol reagents on Jurkat cells and a new thiol-sensitive mutant form of human mitochondrial superoxide dismutase. Hernandez-Saavedra, D., McCord, J.M. Cancer Res. (2003) [Pubmed]
  17. Manganese activation of superoxide dismutase 2 in the mitochondria of Saccharomyces cerevisiae. Luk, E., Yang, M., Jensen, L.T., Bourbonnais, Y., Culotta, V.C. J. Biol. Chem. (2005) [Pubmed]
  18. Reciprocal down-regulation of p53 and SOD2 gene expression-implication in p53 mediated apoptosis. Drane, P., Bravard, A., Bouvard, V., May, E. Oncogene (2001) [Pubmed]
  19. Modulation of antioxidant enzymes p21WAF1 and p53 expression during proliferation and differentiation of human melanoma cell lines. Bravard, A., Petridis, F., Luccioni, C. Free Radic. Biol. Med. (1999) [Pubmed]
  20. Protein kinase D mediates mitochondrion-to-nucleus signaling and detoxification from mitochondrial reactive oxygen species. Storz, P., Döppler, H., Toker, A. Mol. Cell. Biol. (2005) [Pubmed]
  21. Modifications of the anti-oxidant metabolism during proliferation and differentiation of colon tumor cell lines. Bravard, A., Beaumatin, J., Dussaulx, E., Lesuffleur, T., Zweibaum, A., Luccioni, C. Int. J. Cancer (1994) [Pubmed]
  22. Immunohistochemical expression of inducible nitric oxide synthase (iNOS) in human brain tumors: relationships of iNOS to superoxide dismutase (SOD) proteins (SOD1 and SOD2), Ki-67 antigen (MIB-1) and p53 protein. Kato, S., Esumi, H., Hirano, A., Kato, M., Asayama, K., Ohama, E. Acta Neuropathol. (2003) [Pubmed]
  23. Adenovirus-mediated expression of Cu/Zn- or Mn-superoxide dismutase protects against CYP2E1-dependent toxicity. Pérez, M.J., Cederbaum, A.I. Hepatology (2003) [Pubmed]
  24. Adenovirus-mediated wild-type-p53-gene expression sensitizes TNF-resistant tumor cells to TNF-induced cytotoxicity by altering the cellular redox state. Shatrov, V.A., Ameyar, M., Bouquet, C., Cai, Z., Stancou, R., Haddada, H., Chouaib, S. Int. J. Cancer (2000) [Pubmed]
  25. Induction of Mn-superoxide dismutase by tumor necrosis factor, interleukin-1 and interleukin-6 in human hepatoma cells. Ono, M., Kohda, H., Kawaguchi, T., Ohhira, M., Sekiya, C., Namiki, M., Takeyasu, A., Taniguchi, N. Biochem. Biophys. Res. Commun. (1992) [Pubmed]
  26. Expression and regulation of superoxide dismutase activity in human skin fibroblasts from donors of different ages. Allen, R.G., Keogh, B.P., Gerhard, G.S., Pignolo, R., Horton, J., Cristofalo, V.J. J. Cell. Physiol. (1995) [Pubmed]
  27. Identification of nucleophosmin as an NF-kappaB co-activator for the induction of the human SOD2 gene. Dhar, S.K., Lynn, B.C., Daosukho, C., St Clair, D.K. J. Biol. Chem. (2004) [Pubmed]
  28. SOD2: a new type of tumor-suppressor gene? Bravard, A., Sabatier, L., Hoffschir, F., Ricoul, M., Luccioni, C., Dutrillaux, B. Int. J. Cancer (1992) [Pubmed]
  29. No association between SOD2 or NQO1 genotypes and risk of bladder cancer. Terry, P.D., Umbach, D.M., Taylor, J.A. Cancer Epidemiol. Biomarkers Prev. (2005) [Pubmed]
  30. Altered expression profile of superoxide dismutase isoforms in nasal polyps from nonallergic patients. Cheng, Y.K., Hwang, G.Y., Lin, C.D., Tsai, M.H., Tsai, S.W., Chang, W.C. Laryngoscope (2006) [Pubmed]
  31. Anti-inflammatory properties of a chimeric recombinant superoxide dismutase: SOD2/3. Hernandez-Saavedra, D., Zhou, H., McCord, J.M. Biomed. Pharmacother. (2005) [Pubmed]
  32. Polymorphisms in the oxidative stress genes, superoxide dismutase, glutathione peroxidase and catalase and risk of non-Hodgkin's lymphoma. Lightfoot, T.J., Skibola, C.F., Smith, A.G., Forrest, M.S., Adamson, P.J., Morgan, G.J., Bracci, P.M., Roman, E., Smith, M.T., Holly, E.A. Haematologica (2006) [Pubmed]
  33. Polymorphisms in genes related to oxidative stress (MPO, MnSOD, CAT) and survival after treatment for breast cancer. Ambrosone, C.B., Ahn, J., Singh, K.K., Rezaishiraz, H., Furberg, H., Sweeney, C., Coles, B., Trovato, A. Cancer Res. (2005) [Pubmed]
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