Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04179 (MnSOD)
 2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
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.
 ...
PMID:Sequential changes in activities of superoxide dismutase and catalase in brain regions and liver during (-)deprenyl infusion in male rats. 147 83

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.
 ...
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.
 ...
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.
 ...
PMID:Identification and purification of a second form of Cu/Zn superoxide dismutase from Schistosoma mansoni. 150 Jan 73

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.
 ...
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.
 ...
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.
 ...
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.
 ...
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.
 ...
PMID:5-aminolevulinic acid-induced alterations of oxidative metabolism in sedentary and exercise-trained rats. 153 18


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>