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Query: UNIPROT:P04179 (MnSOD)
 2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the pattern of enzymatic antioxidant activities (Cu-Zn superoxide dismutase = SOD, Mn-SOD and glutathione peroxidase = GSH-Px) in brain cortex of rats subjected to experimental induction of subarachnoid hemorrhage (SAH), in order to discuss the modifications of antioxidant systems in relation to the development of lipid peroxidative processes occurring in brain cortex. Lipid peroxidation (quantified as TBRAs content) did not show significantly changes, when sham-operated and SAH rats were compared; meanwhile at 1 hour TBARs content shows an increasing trend both in sham-operated and hemorrhagic rats. The release of leukotriene C4, the major lipoxygenase metabolite, is significantly enhanced at 1, 6 and 48 hours after SAH induction. Cu-Zn SOD activity is significantly reduced at 6 and 48 hours after SAH induction; Mn-SOD activity is significantly affected at 1, 6 and 48 hours after the hemorrhage. GSH-Px activity is significantly reduced only in the late phase (48 hours) after SAH. The results of the present study suggests that: (a) in brain compartment a significant reduction of antioxidant enzymatic activities is related to the increasing trend of enzymatic lipid peroxidation; (b) antioxidant activities showed specific time-dependent modifications: Cu-Zn and Mn SOD activities, which are specific scavengers of superoxide radicals, showed an early impairment, while GSH-Px activity is significantly reduced only after 48 hours; (c) the enhancement of enzymatic lipid peroxidation via the lipoxygenase pathway seems to play a primary role in brain response to SAH. These results should be considered the rationale for pharmacological treatment with antioxidant compounds for brain protection against detrimental effects of subarachnoid hemorrhage.
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PMID:Brain damage following subarachnoid hemorrhage: the imbalance between anti-oxidant systems and lipid peroxidative processes. 150 Sep 55

Superoxide dismutases (SOD) are ubiquitous in aerobic organisms and are believed to play a significant role in protecting cells against the toxic, often lethal, effect of oxygen free radicals. However, direct evidence that SOD does in fact participate in such a protective role is scant. The MnSOD-deficient yeast strain (Sod2d) offered an opportunity to test the functional role of one of several SOD isozymes from the higher plant maize in hopes of establishing a functional bioassay for other SODs. Herein, we present evidence that MnSOD functions to protect cells from oxidative stress and that this function is conserved between species. The maize Sod3 gene was introduced into the yeast strain Sod2d where it was properly expressed and its product processed into the yeast mitochondrial matrix and assembled into the functional homotetramer. Most significantly, expression of the maize Sod3 transgene in yeast rendered the transformed yeast cells resistant to paraquat-induced oxidative stress by complementing the MnSOD deficiency. Furthermore, analyses with various deletion mutants of the maize SOD-3 transit peptide in the MnSOD-deficient yeast strain indicate that the initial portion (about 8 amino acids) of the maize transit peptide is required to direct the protein into the yeast mitochondrial matrix in vivo to function properly. These findings indicate that the functional role of maize MnSOD is conserved and dependent on its proper subcellular location in the mitochondria of a heterologous system.
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PMID:Expression of the maize MnSod (Sod3) gene in MnSOD-deficient yeast rescues the mutant yeast under oxidative stress. 151 16

The developmental expression of catalase, superoxide dismutase (both Mn-SOD and Cu/Zn-SOD) and glutathione peroxide activities were determined in human lung and liver from 10 wk gestation to 3 months following birth. Pulmonary superoxide dismutase and glutathione peroxidase activities did not change appreciably over this period. Catalase activity however, increased from 20.9 +/- 7.8 U/mg protein (n = 29) at 11-20 wk gestation to 73 +/- 27.5 U/mg protein (n = 30; P less than 0.001) following normal delivery (41-60 wk post-conceptual age). Lung catalase activity was temporally associated with the late gestational increase in the fractional content of lung DPPC (r = 0.79, P less than 0.01). In contrast with the lung, liver total superoxide dismutase activity increased from 2.5 +/- 0.6 U/mg protein (n = 27) between 11 and 20 wk gestation to 9.4 +/- 4.4 U/mg protein after term (n = 22; P less than 0.001). Since hepatic Mn-superoxide dismutase activity did not change over this period, the increase was attributed to elevated expression of Cu/Zn-superoxide dismutase. Liver glutathione peroxidase activities remained relatively constant during the same period, while hepatic catalase activity, although constant during gestation (60 +/- 15.6 microU/mg protein), increased significantly following birth (99.7 +/- 33.0 microU/mg protein; P less than 0.001). These results demonstrate that the developmental expression of antioxidant enzymes differs between tissues and that, unlike many commonly used laboratory species, only increased expression of catalase activity is associated with human lung development.
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PMID:Catalase, superoxide dismutase and glutathione peroxidase activities of lung and liver during human development. 152 75

Null mutants of superoxide dismutase (SOD) in Saccharomyces cerevisiae are associated with a number of biochemical defects. In addition to being hypersensitive to oxygen toxicity, strains containing deletions in both the SOD1 (encoding Cu/Zn-SOD) and SOD2 (encoding Mn-SOD) genes are defective in sporulation, are associated with a high mutation rate, and are unable to biosynthesize lysine and methionine. The sod-linked defect in lysine metabolism was explored in detail and was found to occur at an early step in lysine biosynthesis, evidently at the level of the alpha-amino adipate transaminase. To better understand the role of SOD in cell metabolism, our laboratory has isolated yeast suppressors that have bypassed the SOD defect ("bsd" strains), that is, S. cerevisiae cells lacking SOD, yet resistant to oxygen toxicity. Two nuclear bsd complementation groups have been identified, and both suppress a variety of biological defects associated with sod1 and sod2 null mutants. These results demonstrate that a single gene mutation can alleviate the requirement for SOD in cell growth. Both bsd complementation groups are unable to utilize many non-fermentable carbon sources, suggesting a possible suppressor-linked defect in electron transport.
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PMID:Yeast lacking superoxide dismutase. Isolation of genetic suppressors. 152 70

5-Aminolevulinic acid (ALA), a heme precursor that accumulates in acute intermittent porphyria patients and lead-exposed individuals, has previously been shown to autoxidize with generation of reactive oxygen species and to cause in vitro oxidative damage to rat liver mitochondria. We now demonstrate that chronically ALA-treated rats (40 mg/kg body wt every 2 days for 15 days) exhibit decreased mitochondrial enzymatic activities (superoxide dismutase, citrate synthase) in liver and soleus (type I, red) and gastrocnemius (type IIb, white) muscle fibers. Previous adaptation of rats to endurance exercise, indicated by augmented (cytosolic) CuZn-superoxide dismutase (SOD) and (mitochondrial) Mn-SOD activities in several organs, does not protect the animals against liver and soleus mitochondrial damage promoted by intraperitoneal injections of ALA. This is suggested by loss of citrate synthase and Mn-SOD activities and elevation of serum lactate levels, concomitant to decreased glycogen content in soleus and the red portion of gastrocnemius (type IIa) fibers of both sedentary and swimming-trained ALA-treated rats. In parallel, the type IIb gastrocnemius fibers, which are known to obtain energy mainly by glycolysis, do not undergo these biochemical changes. Consistently, ALA-treated rats under swimming training reach fatigue significantly earlier than the control group. These results indicate that ALA may be an important prooxidant in vivo.
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PMID:5-aminolevulinic acid-induced alterations of oxidative metabolism in sedentary and exercise-trained rats. 153 18

Preconditioning the heart with 5 min of ischemia renders the heart very resistant to infarction from subsequent ischemia by an unknown mechanism. We investigated whether the protective effect of preconditioning might be related to an increase in rabbit heart antioxidant defenses. The antioxidant activities of catalase, glutathione peroxidase, Mn superoxide dismutase, Cu,Zn superoxide dismutase, glucose-6-phosphate dehydrogenase, glutathione reductase, and total glutathione were measured in ischemic and normal regions from both control and preconditioned rabbit hearts. All hearts experienced 30 min regional ischemia and 5 min reperfusion. None of the antioxidant enzymes changed in activity when comparing nonischemic and postischemic zones in either nonpreconditioned or preconditioned hearts. Total glutathione, however, was reduced in reperfused zones and showed better preservation in preconditioned hearts. To determine whether this preservation resulted from a higher value at the onset of reperfusion or slower washout during reperfusion, we analyzed a second group of nonreperfused hearts after 30 min ischemia. The hearts had normal glutathione content in both ischemic and nonischemic zones of either preconditioned or control hearts. The most likely explanation is that preconditioned hearts experienced less washout of glutathione simply because they were less injured. We therefore conclude that enhancement of antioxidant defenses is not the mechanism of preconditioning.
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PMID:Protection from reperfusion injury by preconditioning hearts does not involve increased antioxidant defenses. 153 19

We studied the effect of Cu,Zn-superoxide dismutase (SOD) and Mn-SOD, which are specific scavenging enzymes of the superoxide anion radical, on ovulation and examined the localization of SOD in rat ovaries. The results were as follows. 1) The number of ova in the Cu,Zn-SOD (8 mg x 4) administrated group (27.8 +/- 5.4 : p less than 0.01) was significantly reduced compared to the control group (49.0 +/- 3.3). Similarly, the number of ova in the Mn-SOD (2 mg x 2) administrated group (16.9 +/- 7.6 : p less than 0.01) was significantly reduced compared to the control (52.9 +/- 6.3). 2) In the rat ovary, Cu,Zn-SOD examined by the immunohistological method was found to be localized in the granulosa cells of mature Graafian follicles, growing follicles, primordial follicles and epithelial cells of the fallopian tubes. Mn-SOD was localized in the external theca cells of mature Graafian follicles and the corpus luteum. The activity of SOD estimated by the modified nitroblue tetrazolium method was consistent with the immunohistological localization of both SODs. We considered that oxygen radicals and SODs play an important role in rat ovulation, and Cu,ZN-SOD and Mn-SOD have a different localization and action in the rat ovary.
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PMID:[Role of oxygen radical and superoxide dismutase in ovulation in the rat]. 154 52

Four experiments were done to characterize the interactions of copper, iron, and ascorbic acid with manganese in rats. All experiments were factorially arranged Dietary Mn concentrations were less than 1 micrograms/g (Mn0) and 50 micrograms/g (Mn+). Dietary Cu was less than 1 mg/g (Cu0) and 5 micrograms/g (Cu+); dietary Fe was 10 micrograms/g (Fe10) and 140 micrograms/g (Fe140). Ascorbic acid (Asc) was not added to the diet or added at a concentration of 10 g/kg diet. Experiment 1 had two variables, Mn and Cu; in Experiment 2, the variables were Mn and Asc. In Experiment 3, the variables were Mn, Cu, and Asc; in Experiment 4, they were Mn, Cu, and Fe. Definite interactions between Mn and Cu were observed, but they tended to be less pronounced than interactions between Mn and Fe. Cu depressed absorption of 54Mn and accelerated its turnover. In addition, adequate Cu (Cu+), compared with Cu0, depressed liver, plasma, and whole blood Mn of rats. Absorption of 67Cu was higher in animals fed Mn0 diets than in those fed Mn+. Ascorbic acid depressed Mn superoxide dismutase activity and increased Cu superoxide dismutase activity in the heart. The addition of ascorbic acid to the diet did not affect Mn concentration in the liver or blood. Absorption of 54Mn was depressed in rats fed Fe140 compared with those fed Fe10. Interactions among Fe, Cu, and Mn resulted in a tendency for Mn superoxide dismutase activity to be lower in rats fed Fe140 than in rats fed Fe10. Within the physiologic range of dietary concentrations, Mn and Cu have opposite effects on many factors that tend to balance one another. The effects of ascorbic acid on Mn metabolism are much less pronounced than effects of dietary Cu, which in turn affects Mn metabolism less than does Fe.
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PMID:Effects of copper, iron, and ascorbic acid on manganese availability to rats. 154 27

The influence of cytokines on extracellular superoxide dismutase (EC-SOD) expression by human dermal fibroblasts was investigated. The expression was markedly stimulated by interferon-gamma (IFN-gamma), was varying between fibroblast lines stimulated or depressed by interleukin-1 alpha (IL-1 alpha), was intermediately depressed by tumor necrosis factor-alpha (TNF-alpha), and markedly depressed by transforming growth factor-beta (TGF-beta). TNF-alpha, however, enhanced the stimulation by a high dose of IFN-gamma, whereas TGF-beta markedly depressed the stimulations given by IFN-gamma and IL-1 alpha. The ratio between the maximal stimulation and depression observed was around 30-fold. The responses were generally slow and developed over periods of several days. There were no effects of IFN-alpha, IL-2, IL-3, IL-4, IL-6, IL-8, granulocyte-macrophage colony-stimulating factor, human growth hormone, Escherichia coli lipopolysaccharide, leukotriene B4, prostaglandin E2, formylmethionylleucylphenylalanine, platelet-activating factor, and indomethacin. The cytokines influencing the EC-SOD expression are also known to influence superoxide production by leukocytes and other cell types, and the EC-SOD response pattern is roughly compatible with the notion that its function is to protect cells against extracellular superoxide radicals. The results show that EC-SOD is a participant in the complex inflammatory response orchestrated by cytokines. The CuZn-SOD activity of the fibroblasts was not influenced by any of the cytokines, whereas the Mn-SOD activity was depressed by TGF-beta. TNF-alpha, IL-1 alpha, and IFN-gamma stimulated the Mn-SOD activity, as previously known, and these responses were reduced by TGF-beta. The different responses of the three SOD isoenzymes illustrate their different physiological roles.
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PMID:Regulation by cytokines of extracellular superoxide dismutase and other superoxide dismutase isoenzymes in fibroblasts. 155 78

We examined the effect of lipopolysaccharide (LPS) treatment on the expression of manganese and copper/zinc superoxide dismutase (MnSOD and Cu/ZnSOD) mRNA and protein in resident peritoneal macrophages and lung endothelial cells derived from LPS-sensitive (LPS-s) and LPS-resistant (LPS-r) mice. Macrophages from both LPS-s and LPS-r mice treated with LPS for 24 h produced increased levels of MnSOD mRNA and protein. In contrast, levels of lung endothelial cell MnSOD mRNA and protein from LPS-s mice were increased by LPS treatment, while no increases in these parameters were observed in endothelial cells from LPS-r mice. Tumor necrosis factor-alpha (TNF alpha) treatment, however, did increase levels of MnSOD mRNA in both LPS-s and LPS-r endothelial cells to an equal extent. Both macrophage and endothelial cell Cu/ZnSOD mRNA and protein levels were not significantly affected by LPS treatment. These results demonstrate that the mutation that affects susceptibility to LPS in LPS-r mice exerts a differential influence on MnSOD inducibility in a cell specific manner.
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PMID:Mn and Cu/Zn SOD expression in cells from LPS-sensitive and LPS-resistant mice. 155 15


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