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Gene Review

Sod2  -  superoxide dismutase 2, mitochondrial

Mus musculus

Synonyms: MnSOD, Sod-2, manganese SOD, manganese superoxide dismutase
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Disease relevance of Sod2


Psychiatry related information on Sod2


High impact information on Sod2


Chemical compound and disease context of Sod2


Biological context of Sod2


Anatomical context of Sod2


Associations of Sod2 with chemical compounds

  • Here it is shown that Sod2 also serves as a source of the intracellular signaling molecule H(2)O(2) [22].
  • Mortality of Sod2-/- mice increased from 0% in room air to 18 and 83% in 50 and 80% O2, respectively [1].
  • N-acetylcysteine did not alter mortality of Sod2-/- mice [1].
  • Oxidized hydroethidine, 8-hydroxyguanosine immunoreactivity, and nitrotyrosine immunoreactivity were increased in the Sod2 -/+ mice compared with the Wt mice after 3-NP treatment (P < 0.001) [17].
  • METHODS: BMSCs from Sod2(-/-) or Sod2(+/+) mice were cultured with and without adipocytogenic supplements including: 10 mug/mL insulin, 1 muM dexamethasone, and 100 muM indomethacin [19].

Physical interactions of Sod2


Regulatory relationships of Sod2


Other interactions of Sod2

  • Overall, these results indicate that MnSOD regulates both cellular redox status and selectively modulates PKCepsilon signaling, thereby delaying AP-1 activation and inhibiting tumor promotion, resulting in reduction of tumors in MnSOD transgenic mice [24].
  • We observed that E1A blocks induction of MnSOD, IL-6, and FH by TNF-alpha or IL-1alpha [4].
  • Quantitative immunogold ultrastructural analysis confirmed that p53 immunoreactive protein levels were increased to a greater level in the nuclei of epidermal cells from MnSOD KO mice compared to epidermal nuclei from wild type mice similarly treated [29].
  • When cultured cells were subjected to treatment with paraquat to assess their ability to grow in the presence of high levels of superoxide radicals, Sod1-/- cells were 80 times more sensitive and Sod2-/- cells were 12 times more sensitive to paraquat than wild-type cells [30].
  • Selenite prevented nuclear factor-kappaB (NF-kappaB) activation as a mechanism of its inhibitory activity on MnSOD expression in the immune-stimulated cells [31].

Analytical, diagnostic and therapeutic context of Sod2


  1. Increased sensitivity of homozygous Sod2 mutant mice to oxygen toxicity. Asikainen, T.M., Huang, T.T., Taskinen, E., Levonen, A.L., Carlson, E., Lapatto, R., Epstein, C.J., Raivio, K.O. Free Radic. Biol. Med. (2002) [Pubmed]
  2. Pertussis toxin-induced lung edema. Role of manganese superoxide dismutase and protein kinase C. Tsan, M.F., Cao, X., White, J.E., Sacco, J., Lee, C.Y. Am. J. Respir. Cell Mol. Biol. (1999) [Pubmed]
  3. The role of cellular glutathione peroxidase redox regulation in the suppression of tumor cell growth by manganese superoxide dismutase. Li, S., Yan, T., Yang, J.Q., Oberley, T.D., Oberley, L.W. Cancer Res. (2000) [Pubmed]
  4. Coordinate inhibition of cytokine-mediated induction of ferritin H, manganese superoxide dismutase, and interleukin-6 by the adenovirus E1A oncogene. Jennings-Gee, J.E., Tsuji, Y., Pietsch, E.C., Moran, E., Mymryk, J.S., Torti, F.M., Torti, S.V. J. Biol. Chem. (2006) [Pubmed]
  5. Association of a G994-->T missense mutation in the plasma platelet-activating factor acetylhydrolase gene with genetic susceptibility to nonfamilial dilated cardiomyopathy in Japanese. Ichihara, S., Yamada, Y., Yokota, M. Circulation (1998) [Pubmed]
  6. {beta}-Amyloid Mediated Nitration of Manganese Superoxide Dismutase: Implication for Oxidative Stress in a APPNLh/NLh X PS-1P264L/P264L Double Knock-In Mouse Model of Alzheimer's Disease. Anantharaman, M., Tangpong, J., Keller, J.N., Murphy, M.P., Markesbery, W.R., Kiningham, K.K., St Clair, D.K. Am. J. Pathol. (2006) [Pubmed]
  7. A novel neurological phenotype in mice lacking mitochondrial manganese superoxide dismutase. Melov, S., Schneider, J.A., Day, B.J., Hinerfeld, D., Coskun, P., Mirra, S.S., Crapo, J.D., Wallace, D.C. Nat. Genet. (1998) [Pubmed]
  8. Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase. Li, Y., Huang, T.T., Carlson, E.J., Melov, S., Ursell, P.C., Olson, J.L., Noble, L.J., Yoshimura, M.P., Berger, C., Chan, P.H., Wallace, D.C., Epstein, C.J. Nat. Genet. (1995) [Pubmed]
  9. Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Hockenbery, D.M., Oltvai, Z.N., Yin, X.M., Milliman, C.L., Korsmeyer, S.J. Cell (1993) [Pubmed]
  10. The mouse insulin-like growth factor type-2 receptor is imprinted and closely linked to the Tme locus. Barlow, D.P., Stöger, R., Herrmann, B.G., Saito, K., Schweifer, N. Nature (1991) [Pubmed]
  11. The protective role of manganese superoxide dismutase against adriamycin-induced acute cardiac toxicity in transgenic mice. Yen, H.C., Oberley, T.D., Vichitbandha, S., Ho, Y.S., St Clair, D.K. J. Clin. Invest. (1996) [Pubmed]
  12. Mitochondrial manganese superoxide dismutase prevents neural apoptosis and reduces ischemic brain injury: suppression of peroxynitrite production, lipid peroxidation, and mitochondrial dysfunction. Keller, J.N., Kindy, M.S., Holtsberg, F.W., St Clair, D.K., Yen, H.C., Germeyer, A., Steiner, S.M., Bruce-Keller, A.J., Hutchins, J.B., Mattson, M.P. J. Neurosci. (1998) [Pubmed]
  13. Manganese superoxide dismutase protects against 6-hydroxydopamine injury in mouse brains. Callio, J., Oury, T.D., Chu, C.T. J. Biol. Chem. (2005) [Pubmed]
  14. Vasomotor responses in MnSOD-deficient mice. Andresen, J.J., Faraci, F.M., Heistad, D.D. Am. J. Physiol. Heart Circ. Physiol. (2004) [Pubmed]
  15. Multiple deficiencies in antioxidant enzymes in mice result in a compound increase in sensitivity to oxidative stress. Van Remmen, H., Qi, W., Sabia, M., Freeman, G., Estlack, L., Yang, H., Mao Guo, Z., Huang, T.T., Strong, R., Lee, S., Epstein, C.J., Richardson, A. Free Radic. Biol. Med. (2004) [Pubmed]
  16. Selective neuronal vulnerability and inadequate stress response in superoxide dismutase mutant mice. Lynn, S., Huang, E.J., Elchuri, S., Naeemuddin, M., Nishinaka, Y., Yodoi, J., Ferriero, D.M., Epstein, C.J., Huang, T.T. Free Radic. Biol. Med. (2005) [Pubmed]
  17. Involvement of superoxide in excitotoxicity and DNA fragmentation in striatal vulnerability in mice after treatment with the mitochondrial toxin, 3-nitropropionic acid. Kim, G.W., Chan, P.H. J. Cereb. Blood Flow Metab. (2002) [Pubmed]
  18. Spontaneous hypomorphic mutations in antioxidant enzymes of mice. Guo, Z., Higuchi, K., Mori, M. Free Radic. Biol. Med. (2003) [Pubmed]
  19. Adipocyte differentiation in Sod2(-/-) and Sod2(+/+) murine bone marrow stromal cells is associated with low antioxidant pools. Lechpammer, S., Epperly, M.W., Zhou, S., Nie, S., Glowacki, J., Greenberger, J.S. Exp. Hematol. (2005) [Pubmed]
  20. Mitochondrial disease in mouse results in increased oxidative stress. Esposito, L.A., Melov, S., Panov, A., Cottrell, B.A., Wallace, D.C. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  21. Increased oxidative damage is correlated to altered mitochondrial function in heterozygous manganese superoxide dismutase knockout mice. Williams, M.D., Van Remmen, H., Conrad, C.C., Huang, T.T., Epstein, C.J., Richardson, A. J. Biol. Chem. (1998) [Pubmed]
  22. Manganese superoxide dismutase signals matrix metalloproteinase expression via H2O2-dependent ERK1/2 activation. Ranganathan, A.C., Nelson, K.K., Rodriguez, A.M., Kim, K.H., Tower, G.B., Rutter, J.L., Brinckerhoff, C.E., Huang, T.T., Epstein, C.J., Jeffrey, J.J., Melendez, J.A. J. Biol. Chem. (2001) [Pubmed]
  23. Cooperative interaction of NF-kappaB and C/EBP binding sites is necessary for manganese superoxide dismutase gene transcription mediated by lipopolysaccharide and interferon-gamma. Maehara, K., Hasegawa, T., Xiao, H., Takeuchi, A., Abe, R., Isobe, K. FEBS Lett. (1999) [Pubmed]
  24. Overexpression of manganese superoxide dismutase suppresses tumor formation by modulation of activator protein-1 signaling in a multistage skin carcinogenesis model. Zhao, Y., Xue, Y., Oberley, T.D., Kiningham, K.K., Lin, S.M., Yen, H.C., Majima, H., Hines, J., St Clair, D. Cancer Res. (2001) [Pubmed]
  25. Age-related changes in antioxidant enzymes and lipid peroxidation in brains of control and transgenic mice overexpressing copper-zinc superoxide dismutase. Ceballos-Picot, I., Nicole, A., Clément, M., Bourre, J.M., Sinet, P.M. Mutat. Res. (1992) [Pubmed]
  26. A NF-kappaB p65 subunit is indispensable for activating manganese superoxide: dismutase gene transcription mediated by tumor necrosis factor-alpha. Maehara, K., Hasegawa, T., Isobe, K.I. J. Cell. Biochem. (2000) [Pubmed]
  27. Friedreich ataxia: the oxidative stress paradox. Seznec, H., Simon, D., Bouton, C., Reutenauer, L., Hertzog, A., Golik, P., Procaccio, V., Patel, M., Drapier, J.C., Koenig, M., Puccio, H. Hum. Mol. Genet. (2005) [Pubmed]
  28. Nuclear factor-kappaB and manganese superoxide dismutase mediate adaptive radioresistance in low-dose irradiated mouse skin epithelial cells. Fan, M., Ahmed, K.M., Coleman, M.C., Spitz, D.R., Li, J.J. Cancer Res. (2007) [Pubmed]
  29. Manganese superoxide dismutase deficiency enhances cell turnover via tumor promoter-induced alterations in AP-1 and p53-mediated pathways in a skin cancer model. Zhao, Y., Oberley, T.D., Chaiswing, L., Lin, S.M., Epstein, C.J., Huang, T.T., St Clair, D. Oncogene (2002) [Pubmed]
  30. Superoxide-mediated cytotoxicity in superoxide dismutase-deficient fetal fibroblasts. Huang, T.T., Yasunami, M., Carlson, E.J., Gillespie, A.M., Reaume, A.G., Hoffman, E.K., Chan, P.H., Scott, R.W., Epstein, C.J. Arch. Biochem. Biophys. (1997) [Pubmed]
  31. Selenium attenuates expression of MnSOD and uncoupling protein 2 in J774.2 macrophages: molecular mechanism for its cell-death and antiinflammatory activity. Shilo, S., Aharoni-Simon, M., Tirosh, O. Antioxid. Redox Signal. (2005) [Pubmed]
  32. Delayed radioprotection by NFkappaB-mediated induction of Sod2 (MnSOD) in SA-NH tumor cells after exposure to clinically used thiol-containing drugs. Murley, J.S., Kataoka, Y., Cao, D., Li, J.J., Oberley, L.W., Grdina, D.J. Radiat. Res. (2004) [Pubmed]
  33. Inhibition of cell growth in NIH/3T3 fibroblasts by overexpression of manganese superoxide dismutase: mechanistic studies. Li, N., Oberley, T.D., Oberley, L.W., Zhong, W. J. Cell. Physiol. (1998) [Pubmed]
  34. Influence of age and caloric restriction on expression of hepatic genes for xenobiotic and oxygen metabolizing enzymes in the mouse. Mote, P.L., Grizzle, J.M., Walford, R.L., Spindler, S.R. Journal of gerontology. (1991) [Pubmed]
  35. Overexpression of manganese superoxide dismutase selectively modulates the activity of Jun-associated transcription factors in fibrosarcoma cells. Kiningham, K.K., St Clair, D.K. Cancer Res. (1997) [Pubmed]
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