Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04179 (MnSOD)
 2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Superoxide-mediated oxidative stress initiates a chain of events resulting in numerous cellular injuries. We have used genetics and E. coli to investigate the role and regulation of superoxide dismutase (SOD) and its relationship with the other constituents of the oxygen toxicity defence system. Structural SOD genes have been cloned and sequenced, permitting us to refine structural analysis and to isolate SOD-deficient mutants. The conditional oxygen sensitivity of these mutants, together with their increased mutation rate, demonstrated the essential biological role of SOD. Furthermore the complementation of SOD-lacking E. coli deficiencies by introducing a plasmid containing the gene encoding the human SOD supported the proposal that superoxide dismutation is the physiological function of SOD. Regulation of the MnSOD, through which the global SOD level in E. coli is modulated, has been studied using operon and protein fusions with the lactose operon, and led to the conclusion of a multicontrol of MnSOD. Isolation and characterization of regulation mutants are in progress, with the aim of identifying effectors and targets involved in the response to superoxide-mediated oxidative stress.
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PMID:The molecular genetics of superoxide dismutase in E. coli. An approach to understanding the biological role and regulation of SODS in relation to other elements of the defence system against oxygen toxicity. 268 1

The role of antioxidant enzymes, particularly superoxide dismutase (SOD), in immortalization and malignant transformation is discussed. SOD (generally MnSOD) has been found to be lowered in a wide variety of tumor types when compared to an appropriate normal cell control. Levels of immunoreactive MnSOD protein and mRNA for MnSOD also appear to be lowered in tumor cells. Tumor cells have the capacity to produce superoxide radical, the substrate for SOD. This suggests that superoxide production coupled with diminished amounts of MnSOD may be a general characteristic of tumor cells. The levels of MnSOD in certain cells correlates with their degree of differentiation; non-differentiating cells, whether normal or malignant, appear to have lost the ability to undergo MnSOD induction. These observations are used to elucidate a two-step model of cancer. This model involves not only the antioxidant enzymes, but also organelle (particularly mitochondria and peroxisomes) function as a dominant theme in carcinogenesis.
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PMID:Role of antioxidant enzymes in cell immortalization and transformation. 306 20

Cytosolic superoxide dismutase (SOD) activity was found to increase with time during HeLa cell culture, this increase being due exclusively to Mn-SOD. Infection of the cells by Chlamydia trachomatis resulted in a further enhancement of this Mn-SOD activity, whereas cytosolic catalase activity was decreased in these infected cells. Superoxide (O-2.) being able to induce Mn-SOD and to inhibit catalase, these data suggest that Chlamydia trachomatis infection could be responsible for an increase in O-2. production by the infected HeLa cells.
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PMID:[Superoxide dismutase and catalase activity in HeLa 229 cells infected with Chlamydia trachomatis]. 389 44

Superoxide dismutases might conceivably protect against both ionizing radiation and free radical-producing antibiotic antitumor drugs. Copper- and zinc-containing superoxide dismutase (CuZn superoxide dismutase) and manganese-containing superoxide dismutase (Mn superoxide dismutase) were specifically assayed in human malignant tumors and for comparison in human tissues. The tumors possessed less CuZn superoxide dismutase than did the more metabolically active tissues, but there was a large overlap between the tissue and the tumor levels. Mn superoxide dismutase was found in all tumors, and the ratio between the activities of CuZn superoxide dismutase and Mn superoxide dismutase was not different from that of the normal tissues. Human tumors are thus different from tumors from other species which have been reported to be deficient or very low in Mn superoxide dismutase. There was no obvious relation between sensitivity to ionizing radiation and content of the enzymes among the tumors and the tissues, nor did tumor types known to be responsive to radical-producing drugs possess less CuZn superoxide dismutase or Mn superoxide dismutase than other tumors.
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PMID:Copper- and zinc-containing superoxide dismutase and manganese-containing superoxide dismutase in human tissues and human malignant tumors. 724 54

Superoxide dismutases (SODs) scavenge superoxide anion and participate in an essential role as a defense system against oxidative stress in body. Cu,Zn-SOD is localized at cytoplasm. A defect in the Cu,Zn-SOD gene has been demonstrated in some cases of familial amyotrophic lateral sclerosis. Trisomy of chromosome 21 in Down's syndrome increases the level of this isozyme and causes the disease. Inactivation of Cu,Zn-SOD by glycation under hyperglycemic conditions may also be a critical factor for diabetic complication. The expression of the second isozyme, Mn-SOD localized at mitochondrial matrix, is regulated in a complex manner by many stimulants such as interleukin-1, -6, tumor necrosis factor, lipopolysaccharide, and tumor promoters phorbol ester (TPA) and okadaic acid. This isozyme seems to work as a defense mechanism against damage during inflammatory responses. The third isozyme, extracellular SOD, is highly glycosylated and has affinity for heparin sulfate. This may participate in scavenging superoxide in plasma and, therefore, missense mutation in heparin binding domain increases the serum level of this isozyme, although the physiological role is not clearly understood yet.
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PMID:[Physiological significance of superoxide dismutase isozymes]. 760 83

In order to investigate SHR hypertrophied heart myocardial vulnerability, superoxide dismutase, a potent scavenger of superoxide anion, was examined in myocardium of SHR and WKY in relation to aging, as well as under doxorubicin (DOX)-induced cardiomyopathy. Superoxide anion production due to doxorubicin administration was also examined histochemically. Superoxide dismutase (SOD), either as Mn-SOD in mitochondria or as CuZn-SOD in cytoplasm, was found to be lower in aged SHR hypertrophied heart than in age-matched WKY heart. Under DOX-induced cardiomyopathy, SOD activity was significantly lower in SHR hypertrophied heart than either control SHR or treated WKY myocardium. Superoxide anion generation, examined morphologically as formazan deposits, was much more intense in SHR myocardium and some degenerative changes were found such formazan-containing cells. These results clearly indicate that the myocardial vulnerability of SHR hypertrophied heart might be a result of a lowered free radical scavenge ability.
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PMID:Decreased superoxide dismutase activity and increased superoxide anion production in cardiac hypertrophy of spontaneously hypertensive rats. 765 49

Chromosome specific cDNA libraries are a useful source of candidate genes for disorders which have been linked to particular chromosomes. Here, we report the generation of a cDNA library made from a somatic cell hybrid retaining chromosome 6 as its only human component. In order to ascertain the chromosomal location of cDNAs the library was amplified by inter-Alu-PCR and used as probe for competitive in situ suppression (CISS). To identify human specific cDNA clones the library was screened with PD39, a highly human specific Alu consensus probe. Out of 350,000 clones 360 were found to hybridize with PD39. Nucleotide sequences were determined for 40 clones with inserts larger than 500 basepairs (bp) and a sequence comparison was performed at the National Center for Biotechnology Information using BLASTN. One clone was shown to be identical to Manganese Superoxide Dismutase (MnSOD/SOD2) which has previously been assigned to chromosome 6q25. Localization of 11 clones was determined using PCR and clone-specific primer pairs on a hybrid mapping panel DNA set. Two PCR-localized clones and five additional clones were localized by fluorescence in situ hybridization. Transcripts for five clones were identified by RT-PCR. The generation of chromosome 6-specific hncDNAs from a somatic cell hybrid should aid in the identification of disease-associated genes localized on this chromosome.
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PMID:Generation and characterization of a human chromosome 6-specific hncDNA library from a somatic cell hybrid. 769 27

Aerobic life-style offers both benefits and risks to living cells. The major risk comes from the formation of reactive oxygen intermediates (i.e. superoxide radical, O2-; hydrogen peroxide, H2O2; and hydroxyl radical, OH.) during normal oxygen metabolism. However, living cells are able to cope with oxygen toxicity by virtue of a unique set of antioxidant enzymes that scavenge O2- and H2O2, and prevent the formation OH.. Superoxide dismutases (SODs; EC 1.15.1.1) are metalloenzymes essential for aerobic survival. Escherichia coli contains two forms of this enzyme: an iron-containing enzyme (FeSOD) and a manganese-containing enzyme (MnSOD). In E. coli, MnSOD biosynthesis is under rigorous control. The enzyme is induced in response to a variety of environmental stress conditions including exposure to oxygen, redox cycling compounds such as paraquat which exacerbate the level of intracellular superoxide radicals, iron chelation (i.e. iron deprivation), and oxidants. A model for the regulation of the MnSOD has been proposed in which the MnSOD gene (sodA) is negatively regulated at the level of transcription by an iron-containing redox-sensitive repressor protein. The effect of iron-chelation most probably results in removal of the iron necessary for repressor activity. Recent studies have shown that sodA expression is regulated by three iron-dependent regulatory proteins, Fur (ferric uptake regulation), Fnr (fumarate nitrate regulation) and SoxR (superoxide regulon), and by the ArcA/ArcB (aerobic respiration control) system. The potential Fur-, Fnr- and ArcA-binding sites in the sodA promoter region have been identified by using different cis-acting regulatory mutations that caused anaerobic derepression of the gene.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Roles of manganese and iron in the regulation of the biosynthesis of manganese-superoxide dismutase in Escherichia coli. 791 19

Superoxide dismutases (SODs) are vital components in the resistance of aerobic organisms to the toxicity of oxygen. Escherichia coli contains two highly homologous cytoplasmic SODs, a manganese- and an iron-containing enzyme (MnSOD, FeSOD). We previously demonstrated that MnSOD and FeSOD have different physiological functions and that MnSOD is more effective in preventing oxidative damage to DNA. In this report, purified E. coli MnSOD was shown to bind nonspecifically to DNA by electrophoretic mobility shift assay and nitrocellulose-filter binding methodologies. From electrophoretic mobility shift assay, the equilibrium dissociation constants for interaction with a variety of double-stranded and single-stranded oligonucleotides ranged from 1.5 +/- 0.2 to 8.4 +/- 1.3 microM at 20 degrees C. This range of concentrations corresponds to MnSOD concentrations in aerobically grown E. coli. In vivo binding of MnSOD to DNA was supported by colocalization of MnSOD and the E. coli nucleoid in immunoelectron microscopy. Both MnSOD and DNA were inhomogeneously distributed in the cytosol, the concentration of each being higher in the center of the cell and relatively low near the inner membrane. In contrast, there was no evidence for physiologically relevant interaction of FeSOD with DNA. Binding to DNA in vitro was weak, Kd > 40-220 microM, concentrations 7-40 times higher than found in vivo. In addition, the cytoplasmic distribution of FeSOD did not correlate with DNA. FeSOD concentration was higher near the inner membrane and lower in the center of the cytosol. These results demonstrate that E. coli MnSOD associates with DNA in vitro and in vivo. Combined with prior data demonstrating that MnSOD preferentially protects DNA in vivo while an equal enzymatic activity of FeSOD does not (Hopkin, K. A., Papazian, M. A., and Steinman, H. M. (1992) J. Biol. Chem. 267, 24253-24258), our data suggest that E. coli MnSOD acts as a "tethered antioxidant"; association of MnSOD with DNA localizes dismutase activity near a target of oxidative stress and increases protection of DNA from oxidative damage. This model has implications for the therapeutic use of SODs as antioxidants.
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PMID:The manganese superoxide dismutase of Escherichia coli K-12 associates with DNA. 796 11

The NAD(P)H:flavin oxidoreductase (encoded by the fre gene) of Escherichia coli is a soluble enzyme which, under aerobic conditions and together with NAD(P)H and flavins, generates superoxide radicals selectively. This was demonstrated from spin trapping experiments and from the ability of the flavin reductase to achieve a superoxide dismutase (SOD)-sensitive reduction of cytochrome c. The participation of the flavin reductase to O2-. generation in E. coli cells has been studied. Superoxide production in dialyzed cytosolic fraction of SOD-deficient E. coli was stimulated by the addition of flavins. There was no stimulation in soluble extracts of flavin reductase-deficient strains. Moreover, using fusions of sodA promoter to lacZ, we showed that sodA transcription was diminished in flavin reductase-deficient E. coli and that the induction of MnSOD by flavin reductase was SoxRS-independent. These results suggest that the flavin reductase might: (i) in vivo, be an important cytosolic site of O2-. generation; (ii) in vitro, serve as a simple, efficient, and selective O2-. generator.
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PMID:The NAD(P)H:flavin oxidoreductase from Escherichia coli as a source of superoxide radicals. 813 44


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