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)

This study presents an e.s.r. assay for superoxide dismutase (SOD). Enzymic reactions were studied in which Cu,Zn-SOD, Mn-SOD and Fe-SOD each competed with the spin trap 5,5-dimethyl-1-pyrroline 1-oxide (DMPO) for superoxide anion (O2-) at pH 7.8 O2- from dissolved KO2 (potassium superoxide) in dimethyl sulphoxide was added directly to the enzyme solutions containing DMPO. The results show that, in this competition reaction system, the kinetics of the reactions between the enzymes and O2- follow a function y = f[( SOD]0.5). The rate constant, kSOD = 6.4 x 10(9) M-1. S-1, determined for Cu,Zn-SOD is approximately an order of magnitude larger than those for Mn-SOD and Fe-SOD. A comparative study of reported SOD mimics, including Mn2+, MnO2-desferrioxamine mesylate (Desferal) and MnO2-Desferal-ascorbate, was done. The results show that solutions of these complexes are approximately three orders of magnitude less active than Cu,Zn-SOD and approximately two orders of magnitude less active than Mn-SOD or Fe-SOD. The results also suggest that the reactivity toward O2- in solutions of these complexes originates from the Mn2+ present and not from the MnO2-Desferal complexes.
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PMID:Kinetics of superoxide scavenging by dismutase enzymes and manganese mimics determined by electron spin resonance. 131 Nov 75

The antioxidant defenses of the liver, erythrocytes, blood plasma, and interscapular brown adipose tissue (IBAT) of male ground squirrels were compared with those of male rats kept under identical conditions and fed the same diet. Superoxide dismutase (SOD), ascorbate, vitamin E, catalase, glutathione, and enzymes of glutathione metabolism were measured. In general, antioxidant defenses in erythrocytes were lower in ground squirrels than in rats. The same was true in liver, except that catalase-specific activity was higher. In IBAT, ascorbate, vitamin E, catalase, and glutathione reductase were higher than in rat and more of the SOD activity present was cyanide-insensitive (MnSOD). It is suggested that IBAT in ground squirrels may need a relatively greater antioxidant defense because of its important role in thermogenesis, especially in reawakening from hibernation. No major differences in antioxidant defenses between male and female ground squirrels were observed, except that the SOD activity of IBAT was higher in females.
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PMID:Antioxidant defenses in the ground squirrel Citellus citellus. 1. A comparison with the rat. 229 34

The superoxide dismutase produced by Streptococcus mutans OMZ176 during aerobic growth in a chemically defined medium (modified FMC) that was treated with Chelex 100 (to lower trace metal contamination) and supplemented with high purity manganese was purified (162-fold) by heat treatment, ammonium sulfate precipitation, and chromatofocusing chromatography. The superoxide dismutase produced during aerobic growth in the same medium, but without manganese and supplemented with high purity iron, was similarly purified (220-fold). The molecular masses of each holoenzyme were approximately 43,000 with a subunit mass of 20,700, indicating that the enzymes were dimers of two equally sized subunits. The superoxide dismutase from manganese-grown cells was a manganese enzyme (MnSOD) containing 1.2 atoms of manganese and 0.25 atoms of iron/subunit. The superoxide dismutase from iron-grown cells was an iron enzyme (FeSOD) containing 0.07 atoms of manganese and 0.78 atoms of iron/subunit. The amino acid compositions of the MnSOD and the FeSOD were virtually identical, and their amino-terminal sequences were identical through the first 22 amino acids. Dialysis of the FeSOD with o-phenanthroline and sodium ascorbate generated aposuperoxide dismutase with 94% loss of activity; subsequent dialysis of apoenzyme with either manganese sulfate or ferrous sulfate reconstituted activity (recoveries of 37 and 30%, respectively). Electrophoretic determination of cytoplasmic radioiron distribution indicated that (during aerobic growth) manganese prevented insertion of iron into superoxide dismutase, although the iron levels of at least two other cytoplasmic fractions were not altered by manganese. Therefore, S. mutans used the same aposuperoxide dismutase to form either FeSOD or MnSOD, depending upon which metal was available in the culture medium. Such "cambialistic" enzymes (those capable of making a cofactor substitution) may represent a previously unrecognized family of superoxide dismutases.
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PMID:A Streptococcus mutans superoxide dismutase that is active with either manganese or iron as a cofactor. 372 1

During radiotherapy of thoracic tumors, the heart is often included in the primary treatment volume, and chronic impairment of myocardial function occurs. The cellular biomolecules are altered directly by radiation or damaged indirectly by free radical production. The purpose of this investigation was to evaluate the biochemical and functional responses of the rat heart to a single high dose of radiation. The effect of 20 Gy local X irradiation was determined in the heart of Wistar rats under general anesthesia. Mechanical performances were measured in vitro using an isolated perfused working heart model, and cardiac antioxidant defenses were also evaluated. Hearts were studied at 1 and 4 months after irradiation. This single dose of radiation induced a marked drop in the mechanical activity of the rat heart: aortic output was significantly reduced (18% less than control values) at 1 month postirradiation and remained depressed for the rest of the experimental period (21% less than control 4 months after treatment). This suggests the development of myocardial failure after irradiation. The decline of functional parameters was associated with changes in antioxidant defenses. The decrease in cardiac levels of vitamin E (-30%) was associated with an increase in the levels of Mn-SOD and glutathione peroxidase (+45.5% and +32%, respectively, at 4 months postirradiation). However, cardiac vitamin C and catalase levels remained constant. Since these antioxidant defenses were activated relatively long after irradiation, it is suggested that this was probably due to the production of free radical species associated with the development of inflammation.
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PMID:Effect of in vivo heart irradiation on the development of antioxidant defenses and cardiac functions in the rat. 756 73

Male Wistar rats received an aqueous solution of ammonium metavanadate (AMV) of 0.15 mg/V/ml concentration instead of water for 14 days. The erythrocyte count and haemoglobin level in blood were not changed; the haematocrit index was slightly increased. The spontaneous lipid peroxidation in kidney and liver homogenates was increased. The Fe(II)- or ascorbate-induced lipid peroxidation was more pronounced in the kidney than in the liver. No changes in lipid peroxidation were observed in erythrocytes after AMV treatment. The AMV treatment resulted in a decrease in the activity of the antioxidant enzymes, catalase and glutathione peroxidase in the kidney and liver; the cytosolic Cu,Zn-SOD and mitochondrial Mn-SOD were unchanged. The activity of the enzymes in blood was not changed. The results are discussed with a view to the participation of lipid peroxidation in vanadium toxicity.
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PMID:Lipid peroxidation and antioxidant enzymes in vanadate-treated rats. 806 48

A simple method in mice was established to screen anti-ischemic compounds. Thirteen times binding of rubber ring (1 x 1 mm, d = 42 mm) for 4.5 hrs, swelled the paws of 60% mice applied and 14 times binding swelled only of 5% mice. Critically reversible limit lay between these conditions. "All or none" rule dominated the paw swelling perhaps due to different endogenous anti-oxidants' levels of individual mice. Determination of paw reversibility at 90 min of recirculation, was proved to be suitable. Swollen paws at this time returned normal and the paws with no-reflow dropped out by muscle necrosis after several days. Intravenous (i.v.) bovine Cu, Zn-SOD and bacterial Mn-SOD (3-10 x 10(4) U/kg) or liposomal Cu, Zn-SOD (0.3-3 x 10(4) U/kg) were protective (35-50%) by 14 times binding. Allopurinol (10-100 mg/kg) and D-mannitol (3-30 mg/kg) was effective (25-55%). Catalase (i.v., up to 10(5) U/kg) showed little protection, but local injection of 100 U/kg resulted in 50% protection. Glutathione (30 mg/kg) was suppressive only by local injection suggesting the importance of administration route. Desferal, heparin and nitric oxide synthesis inhibitor showed some protection, but indomethacin, mepyramine, ascorbate, vitamin E and dexamethasone were without effect. Excess dosing of all anti-oxidants tested, dramatically decreased their effects demanding caution for therapeutic trials.
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PMID:Superoxide dismutases and anti-oxidants protected mice from no-reflow and necrotic damage induced by ischemia. 831 25

In this study, the activities of major enzymes participating in free radical metabolism (xanthine oxidase, XO; Cu,Zn and Mn superoxide dismutases, SOD; glutathione peroxidase, GSH-Px; catalase, CAT) were measured in kidney tissues from guinea pigs treated with gentamicin alone (200 mg/kg/day), gentamicin plus vitamin C (600 mg/kg/day), gentamicin plus vitamin E (400 mg/kg/day), and gentamicin plus vitamins C and E together for 10 days, and from animals treated with physiological saline solution alone during this period. We found no significant differences between control and gentamicin groups with respect to XO and Cu,Zn-SOD activities. However, the activities of Mn-SOD, GSH-Px, and CAT were found to be significantly depressed in the gentamicin-treated group relative to controls. In the gentamicin plus vitamin C group, the renal tissue Mn-SOD activity was found to be higher as compared with control and gentamicin groups. In this group, XO, GSH-Px and CAT activities were also higher than in the gentamicin-treated group, but no statistically significant differences existed between the values of this group and controls. Similar results were also observed in the gentamicin plus vitamin E group for Mn-SOD, GSH-Px, CAT, and XO. In this group, the Cu,Zn-SOD activity was found to be decreased as compared with control and gentamicin groups. In the gentamicin plus vitamins C and E group, the Cu,Zn-SOD activity was found to be decreased, the XO activity to be unchanged, and Mn-SOD, GSH-Px, and CAT activities to be increased as compared with the gentamicin and control groups. The results suggest that the enzymatic antioxidant defense system was significantly disturbed because of the suppressed activities of Mn-SOD, GSH-Px, and CAT in the kidney tissues from animals treated with gentamicin. However, vitamins C and E given concurrently with gentamicin completely abrogated this enzymatic suppression.
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PMID:Reduced enzymatic antioxidant defense mechanism in kidney tissues from gentamicin-treated guinea pigs: effects of vitamins E and C. 868 38

The superoxide-dismutase (SOD) enzyme, isolated from the halophilic halotolerant bacterium Ba1, was found to be a dimer with a molecular weight of 40 kD and a subunit weight of 23.5 kD. The partial N-terminal sequence showed significant homology to SODs isolated from various sources. Metal analysis showed that SOD from Ba1 contains manganese and iron with the following stoichiometries: 0.9 +/- 0.4 Mn/dimer and 0.6 +/- 0.2 Fe/dimer. Two bands were obtained by isoelectric-focusing, at pI of 4.45 and at 4.40. Native SOD from Ba1 at room temperature was ESR silent. An ESR spectrum of hydrated Mn(II) was obtained from denaturated enzyme. Native enzyme cooled to 97 K showed an ESR spectrum identified as being due to Fe(III). The spectrum was pH-independent. SOD from Ba1 was not inactivated by H2O2. On the basis of these observations, SOD from Ba1 was characterized as MnSOD. The excitation fluorescence spectrum of SOD from Ba1 showed four main peaks in the visible region. The effects on the spectra of KSCN, NaN3, NaF, and ascorbate were examined. Measurements of H2(17)O-nmr relaxation times T1 and T2, for solutions containing E. coli MnSOD and FeSOD, showed no paramagnetic contribution. These results support the assumption that the water molecule at the active site is strongly bound.
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PMID:Mn-superoxide dismutase from the halophilic halotolerant bacterium Ba1--isolation and active site spectroscopic studies. 898 69

Previous studies in conscious pigs have demonstrated that a sequence of ten 2-min coronary occlusion/2-min reperfusion cycles renders the heart relatively resistant to myocardial stunning 24 h later [late preconditioning (PC) against stunning] by an unknown mechanism. Since oxygen radicals contribute importantly to myocardial stunning and since antioxidant enzymes have been reported to be upregulated 24 h after PC in dogs and rabbits, we tested the hypothesis that late PC against stunning is related to an increase in endogenous antioxidant defenses. Chronically instrumented conscious pigs underwent a sequence of ten 2-min coronary occlusion/2-min reperfusion cycles (preconditioned group, n = 11) or received no intervention (control group, n = 5). Twenty-four hours later, pigs were killed and the myocardial levels of Mn superoxide dismutase (SOD), Cu-Zn SOD, catalase, glutathione (GSH) peroxidase, GSH reductase, GSH, GSH disulfide, alpha-tocopherol, and ascorbate were measured. There were no differences in any of the enzymatic or nonenzymatic antioxidants between the ischemic and nonischemic regions in the preconditioned group or between the control and the preconditioned group. Thus, when a marked protection against stunning was present (24 h after PC), no alteration in antioxidant defenses was observed. These results indicate that, in conscious pigs, late PC against myocardial stunning is not mediated by increased endogenous antioxidant defenses, thereby refuting one of the major current hypotheses regarding this phenomenon.
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PMID:Late preconditioning against stunning is not mediated by increased antioxidant defenses in conscious pigs. 936 27

When life first evolved on Earth, there was little oxygen in the atmosphere. Evolution of antioxidant defences must have been closely associated with the evolution of photosynthesis and of O2-dependent electron transport mechanisms. Studies with mice lacking antioxidant defences confirm the important roles of MnSOD and transferrin in maintaining health, but show that glutathione peroxidase (GPX) and CuZnSOD are not essential for everyday life (at least in mice). Superoxide can be cytotoxic by several mechanisms: one is the formation of hydroxyl radicals. There is good evidence that OH* formation occurs in vivo. Other important antioxidants may include thioredoxin, and selenoproteins other than GPX. Nitric oxide may be an important antioxidant in the vascular system. Diet-derived antioxidants are important in maintaining human health, but recent studies employing "biomarkers" of oxidative DNA damage are questioning the "antioxidant" roles of beta-carotene and ascorbate. An important area of future research will be elucidation of the reasons why levels of steady-state oxidative damage to DNA and lipids vary so much between individuals, and their predictive value for the later development of human disease.
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PMID:Antioxidant defence mechanisms: from the beginning to the end (of the beginning). 1051 32


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