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)

Several strains of Bacteroides gingivalis had strong activities of superoxide dismutase (SOD) and were markedly tolerant in the presence of oxygen in 13 strains of black-pigmented Bacteroides species tested. Thus, the strains were maintained and incubated in the either anaerobic or aerobic system. It was found that the SOD activity was significantly induced by oxygen, especially in B. gingivalis 381. The SODs, anaero-SOD and aero-SOD from the extracts of B. gingivalis 381 cells, each was purified by hydrophobic chromatography followed by anion exchange chromatography, and then by gel filtration, respectively. Both the purified enzymes having molecular weight of about 46,000 consisted of two subunits of equal sizes. Spectral analysis revealed that anaero-SOD had the characteristic A350 of Fe-SOD, but aero-SOD exhibited A475 of Mn-SOD. Both samples contained three isozymes with identical isoelectric points of 5.25, 5.10 and 5.00. On the basis of inactivation of SOD by H2O2, it was shown that aero-SOD consisted of one Mn-SOD and a small quantity of two Fe-SODs, whereas anaero-SOD contained only Fe-SOD. To ascertain whether or not the apoprotein of aero-SOD is the same as that of anaero-SOD, each apoprotein was prepared by dialysis in guanidinium chloride plus 8-hydroxyquinoline. Only one protein band with the same isoelectric point of 5.30 on an isoelectric focusing gel was obtained in each purified SOD sample. Subsequent reconstitution of both apoenzymes with either Fe (NH4)2 (SO4)2 or MnCl2 significantly restored their activity. These reconstituted SODs showed only one protein band with SOD activity on Native-PAGE. The complete amino acid sequence of anaero-SOD was determined by automated Edman degradation of the protein, Achrombacter protease I, endoproteinase Asp-N and tryptic digestion. The sequence consisted of 191 residues corresponding to a molecular weight of 21,500 per subunit. Furthermore, the first 36 amino acid sequence of aero-SOD was determined following N-terminal analysis. The two enzymes had similar amino acid compositions, and their amino-terminal sequences were identical through the first 36 amino acids in which methionine residue was present at N-terminal. These results suggest the three isozymes of either anaero-SOD or aero-SOD in B. gingivalis 381 may be formed from the same apoprotein.
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PMID:[Purification, characterization and induction by oxygen of superoxide dismutase from Bacteroides gingivalis 381]. 196 94

We examined the influence of dehydroepiandrosterone (DHEA), a beta-agonist, and exercise training on enzymes that detoxify toxic oxygen species. Feeding 0.4% DHEA decreased hepatic cytosolic (c) selenium-dependent glutathione peroxidase (GPX), (-26%, P less than 0.0001) and increased hepatic mitochondrial (m) Mn superoxide dismutase (SOD), (+38%, P less than 0.001). DHEA decreased myocardial c-GPX (-21%, P less than 0.05) when compared to a beta-agonist (beta A; L644969 Merck and Co.) fed at 5 ppm but neither differed from the Control (C). In contrast, the beta A increased hepatic m-GPX (+25%, P less than 0.05). In skeletal muscle, DHEA and beta A decreased muscle c-GPX by 20 and 12%, respectively (P less than 0.0009). DHEA increased both muscle (+20%, P less than 0.01) and myocardial (+20%, P less than 0.05) c-glutathione S-transferase (GST) over beta A (+20%, P less than 0.01) but neither was significantly different from C. Similar to DHEA, chronic training (Tr) (1 h/day, 5 days/week at 27 m/min, 15% grade on treadmill) decreased hepatic c-GPX (-16%, P less than 0.003). Tr elevates muscle c-GPX (+36%, P less than 0.05) in C. Tr increased myocardial c-GPX by 28% in the beta A-treated rats, whereas Tr decreased myocardial c-GPX by 22% in the C (P less than 0.05, interaction). One hour of acute exercise (Ex) (70% VO2 max relative work load) decreased hepatic homogenate catalase (-12%, P less than 0.02) and increased hepatic m-Mn SOD (+28%, P less than 0.03). Ex decreased myocardial c-GST (P less than 0.05) only in the DHEA-treated rats. DHEA and Tr may improve efficiency of oxygen utilization at the tissue level with lower antioxidant enzyme activity in liver and locally protective up-regulation in muscle. beta A stresses oxygen utilization systems and liver responds by up-regulation of antioxidant enzymes. The increase in myocardial c-GPX activity in the beta A-treated group may be a protective effect against indirect catecholamine-induced myocardial necrosis which results from free radical generation.
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PMID:Dehydroepiandrosterone and a beta-agonist, energy transducers, alter antioxidant enzyme systems: influence of chronic training and acute exercise in rats. 198 Apr 4

Pretreatment or "priming" with vincristine (VcR) has been documented to radioprotect animals from whole body irradiation by accelerating recovery of hematopoietic marrow. The mechanisms underlying this phenomenon are unclear, but the marked similarities between priming with VcR and with immune stimulants such as endotoxin and glucan have led to speculation that VcR may be inducing such radioprotective immunoregulators as interleukin 1 (IL-1) and tumor necrosis factor (TNF). The radioprotective ability of these cytokines, in turn, has been linked to an induction of the antioxidant enzyme manganese superoxide dismutase (Mn SOD). To establish whether priming with VcR is associated with induction of antioxidant enzymes, the activities of Mn SOD, copper-zinc (Cu-Zn) SOD, catalase (CAT), and glutathione peroxidase (GPX) were measured in the marrow of both LLca tumor-bearing and non-tumor-bearing mice given a priming dose of VcR. Results in non-tumor-bearing mice indicate that, similar to IL-1 and TNF administration, VcR treatment increases Mn-SOD activity, but not Cu-Zn SOD, CAT, or GPX activity. Furthermore, this increase occurs at the time VcR priming has been demonstrated previously to exhibit maximal radioprotection, suggesting that it may be contributing factor. However, VcR priming has been demonstrated to radioprotect both tumor-bearing and non-tumor-bearing animals, and no increase in Mn SOD activity (or the other enzymes monitored) was found in the tumor-bearing group. Rather, the presence of tumor significantly suppressed antioxidant enzyme activity. Collectively, the present data suggest that it is unlikely that increased antioxidant enzyme activity is directly involved in the VcR priming response.
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PMID:Marrow antioxidant enzyme activity in tumor-bearing and non-tumor-bearing mice following vincristine treatment. 199 2

The activities of superoxide dismutase (SOD), catalase, glutathione peroxidase, glutathione S-transferases, GSSG reductase, thiol transferases, gamma glutamylcysteine synthetase, and glucose-6-phosphate dehydrogenase, and the concentrations of H2O2 and reduced and oxidized glutathione were determined in the various developmental stages of houseflies. Housefly development was correlated with a progressive increase of cellular oxidizing equivalents and a loss of cellular reducing capacity. The loss of reducing equivalents appeared to result from a decrease in the activity of enzymes involved in glutathione and NADPH synthesis and a concomitant increase in glutathione-oxidizing enzymes. Relatively little change was observed in SOD activity during housefly development; however, the electrophoretic pattern of MnSOD varied in a manner specific to developmental stage. A striking increase in H2O2 concentration occurred prior to pupation possibly due to changes in substrate catabolism. These results support the hypothesis that the cellular environment becomes progressively more oxidizing during development.
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PMID:Developmental patterns in the antioxidant defenses of the housefly, Musca domestica. 199 75

Superoxide dismutase is the main scavenger of superoxide radicals in the mammalian body. The liver has high levels of two types of superoxide dismutase enzymes, cytosolic Cu-Zn and mitochondrial Mn enzymes. The aim of the present study was to investigate the content of two distinct superoxide dismutases in liver during the perinatal transition from a hypoxic to a hyperoxic environment. Both isozymes were purified to homogeneity and used as immunogens in rabbits. Antisera raised were found to recognize only polypeptides of molecular weight 16,900 or 23,400, which correspond to Cu-Zn and Mn superoxide dismutases, respectively. It was found that the level of Cu-Zn superoxide dismutase enzymatic activity and protein as assessed by immunoquantitation increased 10-fold during the postnatal period, reaching adult levels by 3 weeks. In contrast, the amount of Mn superoxide dismutase content increased only twofold to adult levels during the first week of life. Neither of the superoxide dismutases showed an alteration in specific activity or apparent molecular weight in rat livers during ontogeny. These results show that the levels of two intracellular superoxide dismutases are differentially elevated during the perinatal period. It is suggested that each dismutase plays a different physiological role for superoxide scavenging in liver as a function of the hypoxic/hyperoxic environment at birth.
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PMID:Levels of Cu-Zn and Mn superoxide dismutases in rat liver during development. 200 4

Serum concentrations of manganese-containing superoxide dismutase (Mn-SOD; EC 1.15.1.1), a mitochondrial enzyme present in high concentrations in the heart, were measured successively by enzyme immunoassay in 18 patients with acute myocardial infarction (AMI) and in eight with angina pectoris. Results were compared with creatine kinase (EC 2.7.3.2) isoenzyme MB (CK-MB) concentrations in the same specimens. The mean (and SD) serum Mn-SOD concentration in 120 healthy adults was 77.5 (18) micrograms/L. Mn-SOD concentrations exceeding 150 micrograms/L (greater than mean + 4 SD) were considered above-normal. In patients with AMI, the Mn-SOD concentration was 80 (16.8) micrograms/L on admission and increased gradually after the first hospital day. The peak, 260 (109) microgram/L, occurred on the fourth hospital day, at which time the Mn-SOD concentrations in all AMI patients were above normal. Thereafter the Mn-SOD concentration decreased slowly, but still was above normal in 14 of 18 patients on the seventh hospital day. On the other hand, in patients with angina pectoris, the Mn-SOD concentration was 78 (11) micrograms/L on admission and did not increase significantly [peak value 97.5 (42) micrograms/L on the fourth hospital day]. The serum concentration of Mn-SOD is a potentially useful marker for estimating cardiac mitochondrial damage and for diagnosing AMI, especially in the late phase.
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PMID:Concentration of Mn-superoxide dismutase in serum in acute myocardial infarction. 200 57

Human liver manganese superoxide dismutase has been purified by a short procedure that includes a tri-phase partitioning step to provide materials that can be crystallized from ammonium sulfate. X-ray diffraction studies at 3 A resolution show that the crystals belong to the hexagonal space group P6(1)22 or P6(5)22, with cell dimensions a = b = 81.1 A, c = 242.2 A. Manganese superoxide dismutase levels as determined by enzymatic assay as well as by enzyme-linked immunosorbent assay indicated that considerable variations occur in different livers but the total superoxide dismutase activity (Mn superoxide dismutase plus Cu,Zn superoxide dismutase) seems to be kept at constant values.
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PMID:Preparation of human manganese superoxide dismutase by tri-phase partitioning and preliminary crystallographic data. 202 55

Superoxide dismutases (SOD), which are enzymes scavenging the superoxide radical, were studied in two variant lines of the B16 melanoma: B16F1 with low metastatic potential and B16F10 with high metastatic potential. SOD activity was measured by a method utilizing reduction in the chemiluminescence of luminol. Using cell free extracts it was shown that the highly metastatic B16F10 cell line has a SOD activity lower (20.70 +/- 3.07) units/mg protein, n = 8, than that of the less metastatic B16F1 cell line (81.38 +/- 6.78) units/mg protein, n = 8. Acrylamide gel electrophoresis suggested that Mn-SOD activity is higher in B16F1 cells.
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PMID:Lowered superoxide dismutase in highly metastatic B16 melanoma cells. 203 8

The structure of Mn(III) superoxide dismutase (Mn(III)SOD) from Thermus thermophilus, a tetramer of chains 203 residues in length, has been refined by restrained least-squares methods. The R-factor [formula: see text] for the 54,056 unique reflections measured between 10.0 and 1.8 A (96% of all possible reflections) is 0.176 for a model comprising the protein dimer and 180 bound solvents, the asymmetric unit of the P4(1)2(1)2 cell. The monomer chain forms two domains as determined by distance plots: the N-terminal domain is dominated by two long antiparallel helices (residues 21 to 45 and 69 to 89) and the C-terminal domain (residues 100 to 203) is an alpha + beta structure including a three-stranded sheet. Features that may be important for the folding and function of this MnSOD include: (1) a cis-proline in a turn preceding the first long helix; (2) a residue inserted at position 30 that distorts the helix near the first Mn ligand; and (3) the locations of glycine and proline residues in the domain connector (residues 92 to 99) and in the vicinity of the short cross connection (residues 150 to 159) that links two strands of the beta-sheet. Domain-domain contacts include salt bridges between arginine residues and acidic side chains, an extensive hydrophobic interface, and at least ten hydrogen-bonded interactions. The tetramer possesses 222 symmetry but is held together by only two types of interfaces. The dimer interface at the non-crystallographic dyad is extensive (1000 A2 buried surface/monomer) and incorporates 17 trapped or structural solvents. The dimer interface at the crystallographic dyad buries fewer residues (750 A2/monomer) and resembles a snap fastener in which a type I turn thrusts into a hydrophobic basket formed by a ring of helices in the opposing chain. Each of the metal sites is fully occupied, with the Mn(III) five-co-ordinate in trigonal bipyramidal geometry. One of the axial ligands is solvent; the four protein ligands are His28, His83, Asp166 and His170. Surrounding the metal-ligand cluster is a shell of predominantly hydrophobic residues from both chains of the asymmetric unit (Phe86A, Trp87A, Trp132A, Trp168A, Tyr183A, Tyr172B, Tyr173B), and both chains collaborate in the formation of a solvent-lined channel that terminates at Tyr36 and His32 near the metal ion and is presumed to be the path by which substrate or other inner-sphere ligands reach the metal.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Manganese superoxide dismutase from Thermus thermophilus. A structural model refined at 1.8 A resolution. 203 60

Tumor necrosis factor (TNF) facilitates superoxide production, and spin traps may detoxify superoxide by acting as superoxide dismutase mimics. We investigated the ability of a stable nitroxide spin trap, TEMPOL, to protect TNF-sensitive cells from exogenously added TNF. WEHI or L929 cells were incubated with TNF (500 units/ml) for 18 hr either simultaneously with 0 to 8 mM TEMPOL or with the TEMPOL added at varying intervals after TNF exposure. A dose-dependent increase in survival was noted in the TEMPOL-treated cells, with 92 +/- 2% survival of WEHIs treated with 4 mM TEMPOL compared to 26 +/- 1% survival for non-TEMPOL-exposed cells (P2 less than 0.01). Significant increases in survival could be accomplished with as late as 15-hr delayed addition of the compound. The mechanism of protection does not seem to involve newly synthesized protein, and Northern blot analysis revealed that TEMPOL does not induce the genes for MnSOD or Cu-ZnSOD. The ability of TEMPOL to protect against TNF injury, even when exposure is delayed, may prove useful in conditions thought to be associated with free radical-lymphokine interactions such as ischemia-reperfusion, oxygen toxicity, or sepsis.
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PMID:Spin trap protection from tumor necrosis factor cytotoxicity. 203 86


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