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)

We have previously shown that the polyethylene glycol conjugated superoxide dismutase (SOD), which has a plasma half-life of more than 24 h, protects the blood perfused rabbit heart against injury during ischaemia and reperfusion. However, the profile for the dose-dependency of protection was bell-shaped with loss of efficacy below 6000 and above 30,000 U/kg. In the present study, isolated rabbit hearts, perfused with blood from support rabbits, were subjected to a 2 min infusion with St Thomas' Hospital cardioplegic solution followed by 60 min of global ischaemia (37 degrees C) and 60 min of reperfusion. PEG-SOD was administered 1 h or 12-24 h before ischaemia. We assessed the effect of PEG-SOD on ischaemia- and reperfusion-induced changes in: (i) the tissue content of reduced glutathione (GSH), oxidized glutathione (GSSG) and malondialdehyde (MDA) and (ii) the activity of CuZn-SOD, Mn-SOD and glutathione peroxidase and reductase (GPD and GRD). Ischaemia and reperfusion reduced tissue GSH content by 70% and increased GSSG content by 400% (from their fresh aerobic values of 13.1.9 and 0.09 +/- 0.01 nmol/mg protein, respectively). PEG-SOD, given intravenously at various doses to donor and support rabbits 1 h or 12-24 h before ischaemia, protected against these changes with a bell-shaped dose-response relationship. Thus, with 0, 3000, 6000, 12,000, 30,000 and 60,000 U/kg, GSH content was 4.1 +/- 0.4, 4.8 +/- 0.4, 8.5 +/- 0.5, 12.3 +/- 1.6, 12.3 +/- 1.6 and 5.0 +/- 0.5 nmol/mg protein in the 1 h pretreatment group and 4.1 +/- 0.4, 4.2 +/- 0.5, 10.4 +/- 1.5, 11.2 +/- 1.1, 11.4 +/- 0.7 and 4.7 +/- 0.6 nmol/mg protein in the 12-24 h pretreatment group (means +/- S.E.M.). For GSSG the corresponding values were 0.36 +/- 0.04, 0.34 +/- 0.03, 0.12 +/- 0.01, 0.12 +/- 0.01, 0.11 +/- 0.01 and 0.41 +/- 0.03 nmol/mg protein for the 1 h group and 0.36 +/- 0.04, 0.35 +/- 0.02, 0.15 +/- 0.01, 0.12 +/- 0.01, 0.11 +/- 0.01 and 0.34 +/- 0.02 nmol/mg protein for the 12-24 h group. Ischaemia and reperfusion had no effect on tissue MDA content or CuZn-SOD, GDP and GRD activity, and in general, PEG-SOD also lacked significant effect on any of these variables at any dose studied. However, Mn-SOD activity was severely reduced by ischaemia and reperfusion (from 42 +/- 7 U/mg protein in fresh aerobic controls to 6 +/- 1 U/mg protein at the end of reperfusion).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:PEG-SOD and myocardial antioxidant status during ischaemia and reperfusion: dose-response studies in the isolated blood perfused rabbit heart. 143 18

Enzyme activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were determined in the liver as well as several specific brain regions of young and old Fischer-344 rats of both sexes. In the liver of male rats, activities of CAT as well as Mn-SOD were lower, while activities of Cu Zn-SOD were higher in old (30-month-old) rats than in young (7-month-old) ones. Activities of total SOD as well as GSH Px were comparable for young and old male rat livers. In contrast to male rats, in female rat livers, activities of CAT were significantly higher in old (28-months-old) rats, while activities of Mn-SOD were slightly (but significantly) higher in old rat livers. In old male rats, activities of Mn-SOD were significantly higher than in young males in several specific regions of the brain (the substantia nigra (s. nigra), striatum, hippocampus) but lower in the cerebellum. In particular, SOD activities in s. nigra, striatum and hippocampus in old male rats were several fold higher than corresponding values in young male rats. Activities of Cu Zn-SOD were generally unchanged with age. Activities of CAT as well as GSH-Px (both Se-dependent and non-Se-dependent forms) were also relatively unaffected by age. In female rat brains, activities of Mn-SOD as well as those of others all remained mostly unaffected by aging, although there was a general tendency of slightly higher activities in most cerebral regions for Mn-SOD in old female rats. Thus, age-related changes of these antioxidant enzymes in the liver and brain are markedly sex dependent and some enzyme activities (such as CAT in the liver) change in an opposite direction with age. Changes of Mn-SOD in the brain were markedly region-specific in male rats. Results suggest that the significance of the changes of these antioxidant enzyme activities during aging needs to be carefully interpreted, taking into consideration the fact that changes are markedly variable depending on sex as well as the organs and brain regions examined.
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PMID:Age-related changes in antioxidant enzyme activities are region and organ, as well as sex, selective in the rat. 143 48

Superoxide dismutases are enzymes that defend against oxidative stress through decomposition of superoxide radical. Escherichia coli contains two highly homologous superoxide dismutases, one containing manganese (MnSOD) and the other iron (FeSOD). Although E. coli Mn and FeSOD catalyze the dismutation of superoxide with comparable rate constants, it is not known if they are physiologically equivalent in their protection of cellular targets from oxyradical damage. To address this issue, isogenic strains of E. coli containing either Mn or FeSOD encoded on a plasmid and under the control of tac promoter were constructed. SOD specific activity in the Mn and FeSOD strains could be controlled by the concentration of isopropyl beta-thiogalactoside in the medium. The tolerance of these strains to oxidative stress was compared at equal Mn and FeSOD specific activities. Our results indicate that E. coli Mn and FeSOD are not functionally equivalent. The MnSOD is more effective than FeSOD in preventing damage to DNA, while the FeSOD appears to be more effective in protecting a cytoplasmic superoxide-sensitive enzyme. These data are the first demonstration that Mn and FeSOD are adapted to different antioxidant roles in E. coli.
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PMID:Functional differences between manganese and iron superoxide dismutases in Escherichia coli K-12. 144 75

Recent studies have demonstrated that intracolonic administration of trinitrobenzenesulfonic acid (TNB) dissolved in ethanol produces chronic colitis in rats, and that this model shares many features of human inflammatory bowel disease (IBD), particularly Crohn's disease. We investigated the role of free radicals in the pathogenesis of this colitis model. In the early stage of this colitis, antioxidant enzymes (such as superoxide dismutase, glutathione peroxidase) and an antioxidant, alpha-tocopherol, were significantly decreased with the severity of colonic damage. Mn-SOD at a dose of 50000 U/kg attenuated this colitis when preadministered subcutaneously one hour before the induction of colitis. These results suggest that oxygen-derived free radicals may play an important role in this colitis.
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PMID:Possible role of free radicals in the chronic inflammation of the gut. 145 May 97

An in vitro model of alveolar epithelial oxidant injury was developed based on exposure to hyperoxia of cultured guinea pig type II pneumocytes using a biphasic cell culture system in aerobiosis. The present study investigates the roles of intracellular antioxidant enzymes and of glutathione in providing protection against hyperoxia. A 2-day type II cell culture in normoxia was associated with a significant decrease in protein, catalase, and Cu-Zn SOD cell content, whereas ATP cell content, Mn-SOD, and glutathione peroxidase (GPx) activities did not change and glutathione cell content significantly increased. Exposure of type II cells to hyperoxia did not induce significant changes in cell content in protein, SOD, catalase, GPx, or glutathione cell content when compared to control cells (exposed to normoxia). With ATP cell content expressed as a cell injury index (CII), type II cell injury was found to increase with increasing O2 concentrations. Indeed, a 2-day 50% O2 and 95% O2 exposure resulted in a CII of -7.5 +/- 6.2% and 17.9 +/- 5.9%, respectively, LDH release by type II cells was not significantly increased after hypoxic exposure. Cell injury effects of hyperoxia did not correlate with the endogenous antioxidant enzyme activities (SOD, Mn-SOD, catalase). In marked contrast, there was a significant correlation between the CII and total glutathione content of type II cells (p < .01). This correlation was largely due to the close relationship between CII and reduced glutathione. Hyperoxic induced cell injury (as demonstrated by CII > 0) was clearly associated with significantly lower intracellular glutathione level when compared to experiments without hyperoxia induced cell injury (CII < 0). In addition, in the presence of buthionine sulfoximine (BSO), the ability of type II cells to synthetize new glutathione was severely impaired, whereas ATP cell content and cell antioxidant enzyme activities did not change. As a consequence, the reduction of intracellular glutathione significantly increased the susceptibility of cells to hyperoxia injury (p < .05). The results strongly support the hypothesis that the regulation of glutathione levels is an important mechanism in protecting hyperoxia-induced type II cell injury.
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PMID:In vitro effects of hyperoxia on alveolar type II pneumocytes: inhibition of glutathione synthesis increases hyperoxic cell injury. 146 13

A continuous s.c. infusion of (-)deprenyl in young male rats at a dose of 2.0 mg/kg/day for 1 week significantly increased total superoxide dismutase (SOD) activities due to increases in both Cu Zn-SOD and Mn-SOD activities in certain brain regions such as the substantia nitra and striatum, but not in the hippocampus or cerebellum, or in the liver. With continuing infusion, enzyme activities of SOD were further increased in the following weeks, reaching a plateau at 3 weeks. In some cerebral cortices the increase became significant at 3 weeks. In contrast to SOD activities, an increase in catalase (CAT) activity became significant only after 2 weeks of infusion, and only in the brain regions where SOD activities were increased earlier. The delay in the increase in CAT activity following deprenyl infusion suggests that this increased CAT activity is an adaptive response to the earlier increase in deprenyl-induced SOD activities rather than a direct effect of deprenyl on CAT activity, although the latter possibility cannot be excluded.
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PMID:Sequential changes in activities of superoxide dismutase and catalase in brain regions and liver during (-)deprenyl infusion in male rats. 147 83

Evidence is reported that liver manganese deficiency, whether artificially produced by the administration of a Mn-deficient diet, or physiologically occurring in the neonatal life, in mice and rats respectively, causes the down-regulation of the manganese-containing superoxide dismutase at (pre)-transcriptional level. These observations, in addition to previous data concerning Mn-deficiency and the low level of expression of MnSOD in Morris hepatomas, strongly support the role played by the metal ion in the control of the MnSOD by a mechanism of gene activation. While the molecular events taking place in such regulation are not yet identified, the involvement of reactive oxygen species (ROS) as second messengers in the activation of specific transcription factors is suggested.
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PMID:Transcriptional regulation of MnSOD by manganese in the liver of manganese-deficient mice and during rat development. 148 98

The activities of total, Cu,Zn- and Mn-containing superoxide dismutase were studied in the bone marrow of whole-body irradiated rabbits with 6.0 Gy or 24.0 Gy with local shielding. Irradiation with 6.0 Gy depressed the activities of total and Cu,Zn-SOD on the 8th and 15th days, whereas the activity of Mn-SOD did not change. The exposure to 24.0 Gy with local shielding of head and abdominal region decreased Cu,Zn-SOD activity on the 4th and 60th days after irradiation, Mn-SOD activity was lower nearly at all time intervals investigated. The exposure to 24.0 Gy with shielding of whole body without head region increased markedly Cu,Zn-SOD activity, whereas Mn-SOD activity was diminished on the 8th and 15th days after irradiation in comparison with control group. Mn-SOD activity (U per 10(6) of bone marrow cells) was increased at early time intervals, the changes were not so striking after irradiation of rabbits with 24.0 Gy with shielding of whole body without head region.
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PMID:Activity of superoxide dismutase isoenzymes in the bone marrow of irradiated rabbits. 148 2

Effects of cycle ergometer exercise (approximately 75% VO2max for 15 min) on the concentrations of immunoreactive Mn- and CuZn-superoxide dismutases (SOD) in plasma were studied on 10 male students. During the experimental period, Mn-SOD concentration did not vary substantially. On the other hand, CuZn-SOD concentration decreased markedly at 15 min and 24 hr after the exercise; that is, CuZn-SOD appeared to differ virtually from Mn-SOD in recovery pattern.
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PMID:Effects of brief physical exercise on the concentrations of immunoreactive superoxide dismutase isoenzymes in human plasma. 148 53

Our laboratories previously isolated a putative extracellular or membrane-associated Cu/Zn superoxide dismutase (Cu/Zn-SOD) gene, designated a signal peptide-containing (SP) Cu/Zn-SOD, from Schistosoma mansoni. SOD activity was thus investigated throughout the life cycle of S. mansoni and found in all stages: eggs, miracidia, cercariae, schistosomula, lung-stage worms, and adult worms. The adult worms had the highest SOD activity (53 +/- 9 nitrite units), which was five times higher than that of eggs or miracidia and twice as high as that of 3-h-old mechanically transformed schistosomula. Cu/Zn-SOD constituted over 95% of the total SOD activity found in S. mansoni, compared with that of Mn-SOD. Most of Cu/Zn-SOD specific activity was associated with a detergent-extractable fraction of the parasite. Isoelectric focusing gel electrophoresis analysis revealed that there were four major pI variants of Cu/Zn-SOD present in the adult worms. Only two of these Cu/Zn-SOD pI variants were present in the 3-h-old mechanically transformed schistosomula. Fast protein liquid chromatography gel filtration fractionation of adult parasite extract was carried out to correlate the SP Cu/Zn-SOD with the SOD activity by using anti-SP Cu/Zn-SOD monoclonal antibodies, which separated the immunoreactive gene product and the SOD activity into different fractions. Quantitative tissue fractionation also revealed a discordant distribution of the gene product compared with that of Cu/Zn-SOD activity. These results indicated the existence of another Cu/Zn-SOD(s) in the parasite. Purification of the Cu/Zn-SOD activity from the adult worms showed that it represented the two lower-pI variants found in both adult worms and 3-h-old schistosomula. Peptide sequence analysis of the purified Cu/Zn-SOD confirmed that there is a second form of Cu/Zn-SOD in the parasite.
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PMID:Identification and purification of a second form of Cu/Zn superoxide dismutase from Schistosoma mansoni. 150 Jan 73


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