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)

The mechanism whereby tumor necrosis factor (TNF) kills mammalian cells is not well understood, although oxidative damage has been suggested by several investigators. Further, it is not known why cells vary in their responsiveness to TNF. We show that the cytotoxic effect of TNF toward TNF-sensitive L929 cells is blocked under hypoxic conditions, suggesting a critical role of molecular oxygen and reactive oxygen species. To test whether cellular resistance to reactive oxygen species could provide resistance to TNF, we derived a variant strain from L929 cells by chronic exposure to an oxidizing agent, hydrogen peroxide (H2O2). These cells exhibit marked resistance to TNF as well as to H2O2. This cross-protection provides additional evidence that mechanisms of resistance to oxidative damage are causally related to TNF-induced cell death. Scatchard analysis of TNF binding did not reveal significant differences between the H2O2-resistant line and the wild-type L929 line. On the other hand, analyses of antioxidant enzymes and glutathione levels in cells of the wild-type and the H2O2-resistant lines revealed several potentially important differences. Before exposure to TNF, the H2O2-resistant variants have elevated catalase activity, decreased activity of total glutathione-S-transferase (GST), and similar superoxide dismutase (SOD) activities. Exposure to TNF led to alteration in CuZnSOD activity, and much more so in the variants than in the wild-type L929 cells. However, no significant change in MnSOD activities in cells of either cell line was observed. Total GST activity was not altered appreciably by TNF in either cell line, but Western analysis showed that the level of alpha GST isozyme was increased and mu GST isozyme decreased in the H2O2-resistant variants. Furthermore, alterations in total glutathione content were observed in both the control and the variant cells.
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PMID:Hypoxia and resistance to hydrogen peroxide confer resistance to tumor necrosis factor in murine L929 cells. 164 71

The SOD of Propionibacterium freudenreichii, ssp. shermanii belongs to a new group of SOD's capable of retaining activity with either Fe or Mn as active metal cofactor. Both enzymes exhibit identical secondary structure and immunological determinants. Hydrogen peroxide irreversibly inhibits both enzymes. The protein moiety of the Fe- and Mn-SOD could be digested with trypsin to a single active fragment.
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PMID:Comparative studies on a superoxide dismutase exhibiting enzymatic activity with iron and manganese as active cofactor. 164 91

Antioxidant enzyme activities, H2O2 clearance, and H2O2 generation by rat alveolar epithelial type II cells were compared between in situ, freshly isolated (6 h ex vivo), and cultured cells (48 h ex vivo). Immunocytochemical studies did not show changes in catalase, Mn superoxide dismutase, or CuZn superoxide dismutase labeling density in cytoplasm, peroxisomes, or mitochondria. Numbers of peroxisomes and mitochondria per cell decreased in cultured cells. Biochemical studies showed that cell culture resulted in a significant decrease in activities of catalase (49%), glutathione reductase (50%), glutathione peroxidase (74%), and in the capacity of the cells to scavenge extracellular H2O2. Addition of the specific catalase inhibitor, aminotriazole, decreased the rate of consumption of exogenously added H2O2 in freshly isolated cells but not in cultured cells. Neither aminotriazole nor 1,3-bis (2-chloroethyl)-1-nitrosourea, which inactivates glutathione reductase, altered H2O2 consumption by cultured cells. The rate of extracellular H2O2 release in both freshly isolated and cultured cells was 0.71 nmol.min-1.mg protein-1. It can be concluded that levels of some antioxidant enzymes fall in cultured alveolar epithelial type II cells, and that, although catalase likely plays a significant role in protection of freshly isolated cells against oxidant stress, this pathway may be less important after culture.
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PMID:Oxidants and antioxidants in alveolar epithelial type II cells: in situ, freshly isolated, and cultured cells. 173 83

The existence of a relationship between clofibrate-induced peroxisome proliferation and oxidative stress mediated by activated oxygen species was studied in intact peroxisomes purified from Pisum sativum L. plants. Incubation of leaves with 1 mM clofibrate produced a remarkable increase in the peroxisomal activity of acyl-CoA oxidase and, to a lesser extent, of xanthine oxidase, whereas there was a nearly complete loss of catalase activity and a decrease in Mn-superoxide dismutase. Ultrastructural studies of intact leaves showed that clofibrate induced a five- and twofold proliferation of the peroxisomal and mitochondrial populations, respectively, in comparison with those in control leaves. Prolonged incubation with clofibrate produced considerable alterations in the ultrastructure of cells. In peroxisomal membranes, the NADH-induced generation of O2- radicals, as well as the lipid peroxidation of membranes, increased as a result of treatment of plants with clofibrate. In intact peroxisomes treated with this hypolipidemic drug, the H2O2 concentration was higher than in peroxisomes from control plants. These results demonstrate that clofibrate stimulates the production of activated oxygen species (O2- and H2O2) inside peroxisomes, as well as the lipid peroxidation of peroxisomal membranes. This effect is concomitant with a decrease of catalase and Mn-SOD activities, the main peroxisomal enzymatic defenses against H2O2 and O2-, and indicates that in the toxicity of clofibrate, at the level of peroxisomes, an oxidative stress mechanism mediated by activated oxygen species is involved.
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PMID:Peroxisome proliferation and oxidative stress mediated by activated oxygen species in plant peroxisomes. 189 96

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

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

Cu,Zn.superoxide dismutase (SOD) enhanced the toxicity of 3-hydroxyanthranilic acid (3-HAT) to Salmonella typhimurium strain TA 102, evaluated as ability to form colonies. MnSOD showed the same effect. Inactivated Cu.ZnSOD had no effect. SODs accelerated the oxidation of 3-HAT, but inactivated Cu.ZnSOD caused little acceleration. It is proposed that the acceleration of 3-HAT oxidation leads to the enhancement of the 3-HAT toxicity. Catalase protected the bacteria from the toxicity of 3-HAT enhanced by Cu,ZnSOD, indicating that hydrogen peroxide generated in the oxidation of 3-HAT is involved in the toxicity. SODs accelerate the oxidation of 3-HAT and generate more hydrogen peroxide, that causes the enhancement of the 3-HAT toxicity to the bacteria. However, hydrogen peroxide alone was not so toxic. Hydrogen peroxide with 3-HAT was more toxic to the bacteria.
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PMID:Superoxide dismutase enhances the toxicity of 3-hydroxyanthranilic acid to bacteria. 206 Aug 64

Cu,Zn superoxide dismutase (Cu,Zn-SOD; EC 1.15.1.1) is known to be inhibited slowly by H2O2. Using EPR and the spin traps 5,5-dimethyl-1-pyrroline 1-oxide (DMPO) and N-tert-butyl-alpha-phenylnitrone (PBN), we have shown that Cu,Zn-SOD catalyzes the formation of "free" .OH radicals from H2O2 in pH 7.6 bicarbonate buffer. Supporting evidence includes the following: (i) H2O2 and active Cu,Zn-SOD are required to yield significant signals from spin-trap-OH adducts. (ii) With O2-., Cu,Zn-SOD causes the appearance of intense resonance signals due to DMPO-OH adducts. These signals were inhibited strongly by catalase. (iii) With H2O2, Cu,Zn-SOD, and DMPO, radical scavengers formate and azide, but not ethanol, decrease DMPO-OH signals while causing new intense signals due to their corresponding DMPO-radical adducts. Failure of ethanol to quench DMPO-OH signals is discussed in light of the positively charged active channel of the enzyme. (iv) With PBN as a spin trap, ethanol quenches .OH radical signals and yields PBN-trapped hydroxyethyl radical signals. (v) Mn-SOD does not catalyze "free" .OH radical formation and it also exerts no effect on the signals of DMPO-OH adducts when added together with the Cu,Zn-SOD. The capacity of Cu,Zn-SOD to generate "free" .OH radicals from H2O2 may in part explain the biological damage associated with elevated intracellular SOD activity.
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PMID:Copper, zinc superoxide dismutase catalyzes hydroxyl radical production from hydrogen peroxide. 216 16

Superoxide dismutases (SODs) were purified from extracts of either anaerobically maintained or aerated Bacteroides gingivalis. Each purified enzyme (molecular weight, 46,000) was a dimer composed of two subunits of equal sizes. SOD from anaerobically maintained cells (anaero-SOD) contained 1.79 g-atom of Fe and 0.28 g-atom of Mn, and SOD from aerated cells (aero-SOD) contained 1.08 g-atom of Mn and 0.36 g-atom of Fe. Spectral analysis showed that anaero-SOD had the characteristic of Fe-SOD and that aero-SOD had that of Mn-SOD. Both enzyme preparations contained three isozymes with identical isoelectric points. On the basis of inactivation of SOD by H2O2, it was found that aero-SOD consisted of one Mn-SOD and a small quantity of two Fe-SODs, whereas anaero-SOD contained only Fe-SOD. However, each apoprotein from anaero-SOD and aero-SOD, prepared by dialysis in guanidinium chloride plus 8-hydroxyquinoline, showed only one protein band each with the same isoelectric point on an isoelectric focusing gel. Subsequent dialysis of both apoenzymes with either MnCl2 or Fe(NH4)2(SO4)2 restored the activity. These reconstituted SODs showed only one protein band with SOD activity on native polyacrylamide gel electrophoresis. Furthermore, the two enzymes had similar amino acid compositions, and their amino-terminal sequences were identical through the first 12 amino acids. These results suggest that the three isozymes of anaero-SOD and aero-SOD in B. gingivalis are formed from a single apoprotein.
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PMID:Characterization of superoxide dismutases purified from either anaerobically maintained or aerated Bacteroides gingivalis. 230 56

Studies have been conducted to examine the implications of photochemical generation of O2- and its derivatization to H2O2 and OH . in the physiology of the lens in vitro. Physiological status was determined by measuring the uptake of rubidium by the intact tissue when cultured in riboflavin-containing medium, in dark and light, and in the presence and absence of various scavengers. In the presence of light, the uptake of rubidium in the lens was greatly diminished; this suggests photodamage to the tissue. MnSOD and ferricyanide protected against this photochemical damage. The damaging process was thus initiated by the generation of O2-. The tissue damage was also attenuated by catalase, ferrocyanide, and mannitol. These results, therefore, suggest the participation of hydrogen peroxide and the subsequent Haber-Weiss reaction in the photodamaging process.
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PMID:Photodamage to the lens in vitro: implications of the Haber-Weiss reaction. 243 8


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