Disease relevance of SOD2

• Such therapy may prove useful in treatment of human disorders such as sideroblastic anemia, which SOD2 deficiency most closely resembles [1].
• Spontaneously breathing rats were infected with a replication-deficient human type 5 adenovirus containing cDNA for SOD2 [2].
• The expression of superoxide dismutases (SOD) 1 and 2 was studied in 4 clones of human fibroblasts after their infection by simian virus 40 (SV40), in parallel with the alterations of chromosomes 21 and chromosome 6q arms, carrying the genes that encode for SOD1 and SOD2 respectively [3].
• The SOD2 variant has been associated with increased breast cancer risk in two studies [4].
• The fusion gene was expressed in Escherichia coli, and the fully active enzyme SOD2/3 was purified [5].

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

• MnSOD inhibits proline oxidase-induced apoptosis in colorectal cancer cells [11].
• A truncated Tat protein (Tat1-72), known to transactivate the HIV-1 long terminal repeat (LTR), no longer affected Mn-SOD expression, the cellular redox state or TNF-mediated cytotoxicity [12].
• OBJECTIVES: To investigate the influence of a functional polymorphism of the dopamine D3 receptor (DRD3), and assess its interaction with a Mn superoxide dismutase (MnSOD) polymorphism, in contributing to tardive dyskinesia in a chronic inpatient population with schizophrenia [13].
• Pyrrolidine dithiocarbamate (PDTC), an inhibitor of NFkappaB activation, down-regulated the expression and activity of MnSOD, which may suggest that the regulation of MnSOD by IL-1 in retinoic acid-differentiated neuroblastoma cells was mediated by the nuclear factor kappaB [14].
• In the retinoic acid-differentiated neuroblastoma SH-SY5Y cells, IL-1 induced binding activity of NFkappaB and up-regulated the expression and activity of MnSOD [14].

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

• Jurkat cells contain little SOD2 activity, with a different electrophoretic mobility from that of normal lymphocytes [16].
• Because the I58T variant of human SOD2 is thiol-sensitive, we measured SOD in Jurkat cells grown in the presence of thiol agents, observing markedly less SOD activity [16].
• In the two cell lines, the slowing of proliferation coincided with an increase in the activity and amount of immunoreactive superoxide dismutases (SOD1 and SOD2), and a decrease of catalase and glutathione peroxidase activities, and of the glutathione content [19].
• As in established SV40-transformed human fibroblast cell lines, good correlation was found between SOD2 activity and the relative number of 6q arms [3].
• Only SOD2/3 prevented neutrophil accumulation [5].

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].

References