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)

Because superoxide (O2-.) is a mediator of inflammation, Cu,Zn-superoxide dismutase (Cu,Zn-SOD) has been employed as an anti-inflammatory compound. However, Cu,Zn-SOD can increase intra- and extracellular H2O2. This may react with the Cu atom of SOD in a Fenton-type reaction producing the hydroxyl radical (.OH). With a non-physiological concentration of H2O2 (0.8 mmol/l) to stimulate chemiluminescence (CL) at a level < 2 mV, it was observed that the addition of Cu,Zn-SOD (100 micrograms/ml) yielded an increase of 204.7 +/- 78.2 mV (P < 0.05). This increase in CL depended on the concentrations of H2O2 and Cu,Zn-SOD and was only seen with luminol (reacts with O2-. and .OH) but not with lucigenin (reacts with O2-.). No CL was observed when Cu,Zn-SOD was heat inactivated, or when Mn-SOD was used. Dissipators of H2O2, copper chelators and .OH scavengers attenuated this CL. In electron paramagnetic resonance, with the use of the spin-trap dimethylpyrroline-N-oxide (DMPO), it was demonstrated that, in the reaction between H2O2 and Cu,Zn-SOD, .OH was generated. The oxidation of keto-methylthiobutyric acid (KMB) to ethylene, assessed by gas chromatography, demonstrated that H2O2/Cu,Zn-SOD-generated .OH can react with KMB and not only with the SOD molecule itself. We conclude that H2O2 reduces SOD-bound Cu2+ to Cu1+ which, in reaction with H2O2 catalyses its reduction to OH. Whether this 'pro-inflammatory' reaction occurs in vivo remains to be established.
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PMID:Copper, zinc-superoxide dismutase and hydrogen peroxide: a hydroxyl radical generating system. 785 Sep 93

The X-ray structure of the tetrameric iron-dependent superoxide dismutase from Mycobacterium tuberculosis has been refined to an R-factor of 0.167 and a correlation coefficient of 0.954 at 2.0 A resolution. The crystals are monoclinic P2(1) and have four subunits related by strong non-crystallographic 222 (or D2) symmetry in the asymmetric unit. 198 of the 207 amino acids of each subunit are defined by the electron density which shows that they adopt the conserved fold of other iron- or manganese-dependent SODs. The structure can be divided into two domains, the N-terminal domain involving an extended region followed by two projecting antiparallel alpha-helices, and the C-terminal domain containing four more helical segments with a three-stranded antiparallel beta-sheet inserted sequentially between the fourth and fifth helices. The catalytic iron is co-ordinated by five ligands: three histidines (residues 28, 76 and 164), one aspartate (160) and a solvent molecule. The inferred positions of protons at the active site are consistent with the solvent ligand being a hydroxide ion. This ligand interacts with His145 in the Mycobacterium tuberculosis SOD. In the highly homologous Mycobacterium leprae Mn-SOD, the histidine is replaced by glutamine, this being the only significant residue difference within 10 A of the Fe3+. The nature of the amino acid at this position may influence the metal ion specificity of these enzymes. The subunits of the Mycobacterium tuberculosis SOD associate by polar contacts to form dimers, which closely resemble those of other dimeric or tetrameric Fe- or Mn-SODs. However, the dimer-dimer interactions within the tetramer are novel, being dominated by dimerisation of the 144 to 152 loop regions which connect the outer two beta-strands of the three-membered beta-sheet. This contrasts strongly with the other tetrameric Fe- or Mn-SODs where the dimer-dimer association is dominated by the projecting alpha alpha-turn in the N-terminal domain.
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PMID:X-ray structure analysis of the iron-dependent superoxide dismutase from Mycobacterium tuberculosis at 2.0 Angstroms resolution reveals novel dimer-dimer interactions. 787 74

We have characterized the effect of angiotensin converting enzyme (ACE) inhibitors on the activity of CuZn-superoxide dismutase (CuZn-SOD), Mn-superoxide dismutase (Mn-SOD), catalase, and selenium-dependent glutathione peroxidase (Se-GPx). CF1 mice (4-month-old females) were administered water containing enalapril (20 mg/l) or captopril (50 mg/l), during 4 to 11 weeks. After 11 weeks, enalapril treatment caused an increase in the activity of CuZn-SOD, Mn-SOD and Se-GPx, from 19 +/- 4 to 46 +/- 7, 2.1 +/- 0.2 to 3.8 +/- 0.2 units/mg protein and 27 +/- 3 to 54 +/- 3 milliunits/mg protein, respectively. After 11 weeks, captopril treatment increased the activities (P < 0.05) of CuZn-SOD, MnSOD and Se-GPx to 35 +/- 4, 2.9 +/- 0.2 units/mg protein, and 38 +/- 2 milliunits/mg protein, respectively. Catalase activity was not affected by the treatments. These results suggest that ACE inhibitors may protect cell components from oxidative damage by increasing the enzymatic antioxidant defenses.
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PMID:Superoxide dismutase and glutathione peroxidase activities are increased by enalapril and captopril in mouse liver. 789 34

During reperfusion of ischemic brain tissue, the production of reactive oxygen species initiates several modifications of the astroglial functional and ultrastructural integrity. During 24 h after ischemic treatment, modification of cellular superoxide free radical scavenging systems have been observed in primary culture of rat astroglial cell. Mitochondrial Mn superoxide dismutase activity (Mn-SOD) gradually decreases, whereas that of the cytosolic Cu,Zn form of the enzyme remains unaffected. We observed in parallel a significant decrease of glutamine synthetase (GS), an astrocyte specifically located enzyme. Addition of almitrine (dialylamine-4',6'-triazinyl 2')-1-(bis-parafluoro-benzydryl)-4-piperazine or dibucaine (a phospholipase A2 inhibitor) antagonizes the decrease of Mn-SOD activity, but does not affect modification of GS activity. Combined effects are observed by simultaneous addition of both drugs. Our data demonstrate that almitrine may increase the synthesis of some mitochondrial proteins, like Mn-SOD, and provide support for further study on the therapeutic potential of almitrine in ischemic astroglial cell injury.
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PMID:Almitrine prevents some hypoxia-induced metabolic injury in rat astrocytes. 790 67

We measured cerebrospinal fluid (CSF) levels of Cu/Zn superoxide dismutase (Cu/Zn SOD) and Mn superoxide dismutase (Mn SOD) using enzyme immunoassays in 196 neurological patients and 44 controls. The mean Cu/Zn SOD level was 55.8 +/- 27.6 (SD) ng/ml and the Mn SOD, 8.0 +/- 2.5 ng/ml in the controls. Cu/Zn SOD or Mn SOD levels showed neither age-nor sex-related differences in the controls. Both SODs were markedly elevated in cerebrovascular diseases, bacterial meningitis and encephalitis. Mn SOD alone was significantly elevated in neurodegenerative diseases. We compared SODs with CSF levels of neuron-specific enolase (NSE) and S-100b protein (S-100b) in cerebral infarction and bacterial meningitis. Both SODs were correlated with NSE and S-100b in patients with cerebral infarction, but not in those with bacterial meningitis. This means that elevations of SODs in CSF may not only be due to leakage from damaged nervous tissues, but also to the induction of SOD in lesions. We conclude that the mean SOD levels were elevated in various neurological diseases, and their varied magnitudes may be associated with the underlying diseases.
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PMID:Cerebrospinal fluid levels of superoxide dismutases in neurological diseases detected by sensitive enzyme immunoassays. 793 17

1. Control and copper-deficient rats were treated with: (i) indomethacin; (ii) indomethacin in the presence of cimetidine; and (iii) indomethacin in the presence of Cu(cimetidine)2. The levels of copper, zinc and manganese as well as the nature of superoxide dismutase activity in the liver were studied. 2. Copper deficiency caused a decrease of enzyme SOD activity, EDTA-insensitive (by 84%) and the appearance of nonenzyme SOD-like activity, EDTA-sensitive. The levels of copper and zinc decreased by 67% and 40% and the manganese level increased by 53%. 3. The above-mentioned treatments (i, ii, iii) of copper-deficient rats induced a progressive increase of enzyme SOD activity (by 19, 90 and 176%, respectively) without, however, changing nonenzyme SOD-like activity. It was only indomethacin treatment in the presence of Cu(cimetidine)2 that increased the copper level in control (by 82%) and copper-deficient (by 182%) rats. 4. The liver contained 4 CuZnSOD- and 1 MnSOD-isoenzymes, whose number and position on the gel were affected neither by copper deficiency nor by indomethacin treatment in the presence of Cu(cimetidine)2. Copper deficiency significantly increased the MnSOD-band and reduced the CuZnSOD-bands, particularly that with pI approximately 5.7. Indomethacin in the presence of Cu(cimetidine)2 changed neither the MnSOD-band nor the reduced CuZnSOD-band with pI approximately 5.7, but restored to normal all the other CuZnSOD-bands.
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PMID:Do indomethacin and cimetidine or Cu(cimetadine)2 affect the nature of superoxide dismutase activity in the liver of copper-deficient rats? 795 24

Treatment of cells or organisms with agents that increase the expression of MnSOD confers resistance to certain types of oxidative damage. However, since these treatments also affect other cellular systems with antioxidant capabilities, the role of MnSOD remains uncertain. To better determine whether increased MnSOD expression confers increased resistance to oxidant stress, a eukaryotic expression vector harboring a mouse MnSOD cDNA was constructed. Bovine lung microvessel endothelial cells were co-transfected with the MnSOD expression vector and pSV2-neo, which contains the neor gene and provides a dominant selectable marker. Control clones were generated by transfecting the cells with psV2-neo alone. Stably transfected cell lines were selected and cell lines overexpressing MnSOD were confirmed by Northern blotting, immunoblot analysis, and activity gels. The activities of copper/zinc superoxide dismutase, catalase, and glutathione peroxidase were examined, and no increase in activity of any of these enzymes was detected. Cells were exposed to hyperoxic challenge by treatment with 95% O2 and 5% CO2 for 24 h. Viability was assessed by a clonogenic assay. The cell lines that overexpressed MnSOD showed a twofold increase in survival compared to control cells. These results demonstrate a significant resistance to hyperoxia induced oxidative stress in endothelial cells overexpressing MnSOD.
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PMID:Overexpression of manganous superoxide dismutase (MnSOD) in pulmonary endothelial cells confers resistance to hyperoxia. 796 7

Cultured rat glomerular mesangial and epithelial cells and bovine glomerular endothelial cells were exposed to various concentrations of hydrogen peroxide (H2O2). Mesangial cells treated with 10 to 100 microM H2O2 for 24 hours showed a two- to ninefold increase in Mn-SOD mRNA expression associated with significantly (P < 0.005) increased Mn-SOD activity (22.2 +/- 1.2 and 12.2 +/- 0.7 mu/mg protein for H2O2 100 microM treated and untreated cells, respectively). In contrast, expression of Cu-Zn SOD and beta-actin mRNA was not affected by H2O2. Induction of Mn-SOD mRNA by H2O2 was inhibited by actinomycin-D (4 microM) treatment. Glomerular endothelial cells also showed an increase in Mn-SOD mRNA expression following 100 microM H2O2 treatment, as did glomerular epithelial cells following treatment with 500 and 1000 microM H2O2 but not with 100 microM. Transcriptional activity of the Mn-SOD gene was assessed with a fusion reporter gene consisting of a luciferase gene (pGL2P) and a 1.2 kb fragment from the rat Mn-SOD genomic DNA (-806 to +408 bp of the transcription initiation site, -806:+408). The construct was transfected into rat glomerular mesangial and epithelial cells. Mesangial and epithelial cells transfected with pGL2P (-806:+408) and treated with H2O2 (100 microM and 1 mM for mesangial and epithelial cells, respectively) demonstrated some threefold increase in luciferase activity, whereas cells transfected with pGL2P lacking the Mn-SOD fragment did not show changes in luciferase activity following H2O2 treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxidants induce transcriptional activation of manganese superoxide dismutase in glomerular cells. 796 52

We previously found that low-dose X-ray irradiation or radon (weak alpha-ray) inhalation increases SOD activities and reduces lipid peroxide levels in various organs of 7-week-old rats or rabbits. In this study, we examined how the changes of SOD activity, lipid peroxide level, and membrane fluidity of the cerebral cortex in aged male Wistar rats (65 and 91 weeks old) were affected by low-dose X-ray irradiation (100 cGy or under) compared with those in 7-week-old rats, to elucidate the mechanism of aging inhibition. The following results were obtained: Although radiation sensitivity was observed to decreases with age, low-dose irradiation changed the Mn-SOD activity, lipid peroxide level, and membrane protein fluidity parameter of the cerebral cortex in the age rats to be closer to those in the youth. These findings suggest that the increased SOD activity induced by low-dose irradiation enhances biomembrane functions, and that the decrease of lipid peroxide level enhances the membrane protein fluidity.
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PMID:Effects of low-dose X-ray irradiation on biomembrane in brain cortex of aged rats. 800 39

We have previously demonstrated that intratracheal (IT) but not intraperitoneal (IP) administration of 5 micrograms tumor necrosis factor (TNF) or interleukin-1 (IL-1) selectively enhances pulmonary Mn superoxide dismutase (Mn SOD) mRNA, leading to increased Mn SOD protein and enzyme activity, and protects rats against O2 toxicity. In this study, we demonstrated that enhancement of pulmonary Mn SOD mRNA by TNF or IL-1 was highly dependent on the route of administration. IT insufflation of 5 micrograms TNF or IL-1 selectively enhanced levels of pulmonary but not splenic or renal Mn SOD mRNA. In contrast, IP or intravenous (i.v.) administration of TNF (5 micrograms) or IL-1 (5, 20, or 50 micrograms) had little or no effect on levels of Mn SOD mRNA in the lung, spleen, or kidney. Both TNF and IL-1, whether given by IT, IP, or i.v. administration, had no effect on levels of Cu, Zn SOD mRNA. IP administration of 2 mg/kg actinomycin D 2 h before IT insufflation of IL-1 paradoxically increased the level of pulmonary Mn SOD mRNA without affecting the level of Cu,Zn SOD or beta-actin mRNA in IL-1-treated rats. Nuclear runoff transcription assay revealed that IT insufflation of IL-1 enhanced the rate on MN SOD but not Cu,Zn SOD mRNA synthesis. We conclude that IL-1-induced increase in pulmonary Mn SOD mRNA is at least in part regulated at the transcriptional level.
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PMID:Induction of pulmonary Mn superoxide dismutase mRNA by interleukin-1. 802 55


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