UNIPROT:P04179 - FACTA Search

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

Scrapie, one of the prion diseases, is a transmissible neurodegenerative disease of sheep and other animals. Clinical symptoms of prion diseases are characterized by a long latent period, followed by progressive ataxia, tremor, and death. To study the induction of neurodegeneration during scrapie infection, we have analyzed the activities of various antioxidant enzymes and mitochondrial enzymes in cerebral cortex, brain stem, and cerebellum of scrapie-infected hamsters. The activity of mitochondrial Mn-superoxide dismutase (SOD) was decreased, while the activities of cytosolic Cu/Zn-SOD and catalase were not altered in infected brains. The activities of glutathione peroxidase and glutathione reductase were increased in scrapie-infected hamsters. The decreased activity of Mn-SOD might result in increasing oxidative stress in the mitochondria of infected brain; this concept is supported by our findings of a high level of lipid peroxidation, and low levels of ATPase and cytochrome c oxidase activity in the infected cerebral mitochondria. In addition, structural abnormalities of mitochondria have been observed in the neurons of hippocampus and cerebral cortex of infected brain. These results suggest that mitochondrial dysfunction caused by oxidative stress gives rise to neurodegeneration in prion disease.
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PMID:Mitochondrial dysfunction induced by oxidative stress in the brains of hamsters infected with the 263 K scrapie agent. 975 61

The present study further investigates evidence for lipid peroxidation in atherosclerotic aortic tissue by determining the activity of antioxidant enzymes and concentrations of lipid peroxide fluorochromes in abdominal aortas from 15 patients with abdominal aortic aneurysms (AAA), an additional 7 patients with ruptured abdominal aneurysms, and 12 patients with atherosclerotic occlusive disease (AOD). Aortas from nonatherosclerotic organ donors served as nondiseased controls. Cu, Zn-superoxide dismutase (Cu,Zn-SOD) activities in AAA and AOD tissues were 16% and 25% of control activity, respectively. Mn-SOD activity in diseased aortae were about 65% of controls. CuZn-SOD protein in AAA and AOD was 56% and 100% of controls, respectively, resulting in significantly lower CuZn-SOD specific activity in these tissues. Ruptured AAA tissue also had low SOD activity and protein. Glutathione peroxidase (GPx) activity in AAA and AOD aortas was 70% and 65% of controls, respectively, and glutathione reductase (GR) activity in AAA and AOD aortas was 80% and 65% of control activities, respectively. These results were associated with significantly higher lipid peroxide fluorochromes, expressed as U/g aorta, in both groups of atherosclerotic aortas than in controls. AOD aortas had 33% higher fluorescence than AAA aortas, but the highest levels were seen in ruptured AAA. These data further support the involvement of free radicals and lipid peroxidation in atherosclerotic aortic disease, but do not indicate that these mechanisms are specifically involved in aneurysm formation versus development of occlusive disease.
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PMID:Antioxidant enzyme activity in human abdominal aortic aneurysmal and occlusive disease. 989 67

Alzheimer's disease (AD) has been hypothesized to be associated with oxidative stress. In this study, the expression of key oxidative stress-handling genes was studied in hippocampus, inferior parietal lobule, and cerebellum of 10 AD subjects and 10 control subjects using reverse transcriptase-polymerase chain reaction (RT-PCR). The content of Mn-, Cu,Zn-superoxide dismutases (Mn- and Cu,Zn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione reductase (GSSG-R) mRNAs, and the "marker genes" (beta-actin and cyclophilin) mRNAs was determined. This study suggests that gene responses to oxidative stress can be significantly modulated by the general decrease of transcription in the AD brain. To determine if the particular oxidative stress handling gene transcription was induced or suppressed in AD, the "oxidative stress-handling gene/beta-actin" ratios were quantified and compared with control values in all brain regions studied. The Mn-SOD mRNA/beta-actin mRNA ratio was unchanged in all regions of the AD brain studied, but an increase of the Cu,Zn-SOD mRNA/beta-actin mRNA ratio was observed in the AD inferior parietal lobule. The levels of peroxidation handling (CAT, GSHPx, and GSSG-R) mRNAs normalized to beta-actin mRNA level were elevated in hippocampus and inferior parietal lobule, but not in cerebellum of AD patients, which may reflect the protective gene response to the increased peroxidation in the brain regions showing severe AD pathology. The results of this study suggest that region-specific differences of the magnitude of ROS-mediated injury rather than primary deficits of oxidative stress handling gene transcription are likely to contribute to the variable intensity of neurodegeneration in different areas of AD brain.
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PMID:The expression of key oxidative stress-handling genes in different brain regions in Alzheimer's disease. 1009 42

Because programmed cell death (PCD) is an important mode of pericyte dropout in human diabetic retinopathy, whether increased oxidative stress in cells with diminished antioxidant defenses plays a causative role in the PCD process in diabetic pericytes has been studied. Ten diabetic and eight non-diabetic eye-bank eyes from 5 diabetic and 4 non-diabetic patients were included in this study. From individual neural retinas pericytes were isolated by a newly developed immunomagnetic technique. Total mRNA of the purified pericytes was isolated for quantitative reverse transcriptase (RT)-PCR assay. mRNA levels of a death protease (CPP32), the major enzyme that initiates the proteolytic cascade leading to cell death, were determined in association with the expression of antioxidative enzymes including glutathione peroxidase (GSH-Px), glutathione reductase, CuZn superoxide dismutase (SOD), MnSOD and catalase genes in pericytes. In comparison with pericytes from non-diabetic retinas, pericytes from diabetic retinas highly expressed CPP32 genes (4 +/- 0.6 fold increase, p < 0.01, n = 9). In diabetic pericytes, up-regulation of glutathione peroxidase (GSH-Px) (8.2 +/- 0.9 fold increase, p < 0.01, n = 9) and down-regulation of glutathione reductase (Gr) (4.1 +/- 0.4 fold decrease, p < 0.05, n = 9) and CuZnSOD (2.1 +/- 0.7 fold decrease, p < 0.05, n = 9) were observed. mRNA levels of MnSOD and catalase of diabetic pericytes did not differ significantly from those of non-diabetic pericytes. Overexpression of a member of interleukin-1 beta-converting enzyme (ICE) family, CPP32, indicated that the pericytes from diabetic retinas are in a "pre-PCD" state. This is the first evidence that the ICE family of death proteases is involved in pericyte dropout in diabetes. In these pre-PCD cells, the expression of antioxidant enzyme genes also was changed. Up-regulation of GSH-Px indicates a compensation mechanism to meet the demand of excessive glutathione in reduced form. Decreased levels of both glutathione reductase and CuZnSOD, despite the oxidative stress in the diabetic condition, suggest the breakdown of the antioxidant defense in pericytes. Most importantly, the altered gene profile of scavenging enzymes under diabetic conditions, correlating with overexpression of the cell death protease gene, together suggest increased oxidative stress as an etiological agent of pericyte dropout in diabetic retinopathy.
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PMID:Altered mRNA levels of antioxidant enzymes in pre-apoptotic pericytes from human diabetic retinas. 1009 40

The purpose of this study was to evaluate rat tissue antioxidant status after repeated administration of d-amphetamine. Three groups of four rats each were used: control, d-amphetamine sulphate dosed (s.c., 20 mg/kg per day), and pair-fed. After 14 days of d-amphetamine daily administration, superoxide dismutase (CuZnSOD and MnSOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GRed), glutathione-S-transferase (GST), glutathione (GSH), cysteine and thiobarbituric acid reactive substances (TBARS) were measured in liver, kidney, and heart. Various serum and urine parameters were also analysed. d-Amphetamine treatment induced an increase of liver GSH, as well as a decrease of cysteine and MnSOD levels in this organ. A small increase in serum transaminases was also observed in comparison to the pair-fed group. Hepatic levels of TBARS, GPx, GRed and CuZnSOD were found to be similar among the three groups of rats. d-Amphetamine treatment induced an increase of kidney GST, GRed and catalase levels, and an elevation of N-acetyl-beta-D-glucosaminidase efflux to the urine, accompanied by a decrease in urinary creatinine, compared to the pair-fed group. In d-amphetamine treated animals, heart cysteine levels were significantly depleted when compared to the pair-fed group, but all three groups of rats were found to have similar heart antioxidant enzyme levels. These results indicate that repeated administration of d-amphetamine caused a certain degree of stress in liver and kidney, which was followed by adaptations of antioxidant defences. The mechanisms involved in d-amphetamine-induced toxicity may explain the different adaptations observed for the studied organs.
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PMID:Effect of d-amphetamine repeated administration on rat antioxidant defences. 1035 Jan 88

This study tested whether a strain of heterozygous Mn superoxide dismutase (SOD) knockout mice differed from wild types in response to lethal (100 or 85%) or sublethal (50 or 75%) oxygen exposures. Lung MnSOD activity was significantly (-40%) less in the heterozygous mice, and lung catalase activity was also significantly decreased. Total SOD activity, glutathione peroxidase, and glutathione reductase did not differ between heterozygous (+/-) and wild-type (+/+) mice. We exposed both heterozygous and wild-type mice to hyperoxia (50, 75, 85, or 100% oxygen) until death or for 48 hours to assess sublethal lung injury. Survival of the heterozygous and wild-type mice did not differ significantly in 100 or 85% oxygen. No mice of either genotype died in 50 or 75% oxygen (14-day exposures). Hyperoxia exposures significantly increased (by two-way ANOVA) the alveolar lavage protein concentration, percent neutrophils, and lung wet-dry/dry weight ratios. No significant differences occurred between the heterozygous and wild-type mice for any marker of injury at any oxygen level. Lavage fluid total nitrite concentrations did not differ at any oxygen level. Hyperoxia caused a similar degree of nitration of lung structural proteins detected by immunohistochemistry in both groups.
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PMID:Survival, lung injury, and lung protein nitration in heterozygous MnSOD knockout mice in hyperoxia. 1059 22

Previous studies have suggested that reactive oxygen species (ROS) are mediators in the teratogenic process of diabetic pregnancy. In an animal model for diabetic pregnancy, offspring of the H rat strain show minor dysmorphogenesis when the mother is diabetic, whereas the offspring of diabetic rats of a sister strain, U, display major morphologic malformations. Earlier studies have shown that embryonic catalase activity is higher in the H than in the U strain, and maternal diabetes increases this difference in activity. The aim of this study was to characterize the influence of genetic predisposition on diabetic embryopathy by comparing the mRNA levels of ROS-metabolizing enzymes in the two strains. We determined the mRNA levels of catalase, glutathione peroxidase, gamma-glutamylcystein-synthetase, glutathione reductase, and superoxide dismutase (CuZn-SOD and Mn-SOD) in day 11 embryos of normal and diabetic H and U rats using semiquantitative reverse transcription-polymerase chain reaction. The mRNA levels of catalase and Mn-SOD were increased in H embryos as a response to maternal diabetes, and no differences were found for the other genes. Sequence analysis of the catalase promoter indicated that the difference in mRNA levels may result from different regulation of transcription. Sequence analysis of the catalase cDNA revealed no differences between the two strains in the translated region, suggesting that the previously observed difference in the electrophoretic mobility in zymograms is due to posttranslational modifications. An impaired expression of scavenging enzymes in response to ROS excess can thus be an integral part of a genetic predisposition to embryonic dysmorphogenesis.
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PMID:Increased mRNA levels of Mn-SOD and catalase in embryos of diabetic rats from a malformation-resistant strain. 1061 56

The erythroid differentiation of K562 cells could be achieved by exposure to several pharmacologic agents, including hemin, butyric acid (BA), and anthracycline antitumor drugs such as aclarubicin (ACLA) and doxorubicin (DOX). When used at subtoxic concentrations, these drugs induce the overexpression of erythroid genes, leading to hemoglobinization of cells. Because anthracyclines are known to generate oxidative damage, we intended to demonstrate the involvement of an oxidative stress in the chemically induced differentiation process. The addition of antioxidants to anthracycline- and BA-induced cells decreased their growth and dramatically reduced the percentage of differentiated cells at day 3. Northern blot analysis showed that antioxidants also decrease the expression of erythroid genes and related transcription factors in induced cells. Moreover, analyses of oxidative stress markers showed that treatment with BA, ACLA, and DOX lead to a decrease in reduced glutathione and antioxidant enzymes (glutathione peroxidase [GPx], glutathione reductase [GRase], CuZn superoxide dismutase [SOD], and catalase [CAT]). In addition, DOX increased thiobarbituric acid reactants (TBARs), and MnSOD activity was decreased by BA and DOX. Finally, the production of reactive oxygen species (ROS) by differentiating agents was demonstrated using the dihydroethidium probe in a microspectrofluorometric assay. Altogether, these results strongly suggest the involvement of an oxidative stress generated by BA or anthracyclines as the first step in the irreversible differentiation process. Additionally, these results underline the differences between BA, ACLA, and DOX molecular mechanisms.
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PMID:Oxidative stress involvement in chemically induced differentiation of K562 cells. 1065 87

The effect of growing pea plants with 50 microM CdCl2 on the activated oxygen metabolism was studied at subcellular level in peroxisomes isolated from pea leaves. Cadmium treatment produced proliferation of peroxisomes as well as an increase in the content of H2O2 in peroxisomes from pea leaves, but in peroxisomal membranes no significant effect on the NADH-dependent O2*- production was observed. The rate of lipid peroxidation of membranes was slightly decreased in peroxisomes from Cd-treated plants. This could be due to the Cd-induced increase in the activity of some antioxidative enzymes involved in H2O2 removal, mainly ascorbate peroxidase and glutathione reductase, as well as the NADP-dependent dehydrogenases present in these organelles. The activity of xanthine oxidase did not experiment changes by Cd treatment and this suggests that O2*- production in the peroxisomal matrix is not involved in Cd toxicity. This was supported by the absence of changes in plants treated with Cd in the Mn-SOD activity, responsible for O2*- removal in the peroxisomal matrix. Results obtained indicate that toxic Cd levels induce imbalances in the activated oxygen metabolism of pea leaf peroxisomes, but its main effect is an enhancement of the H2O2 concentration of these organelles. Peroxisomes respond to Cd toxicity by increasing the activity of antioxidative enzymes involved in the ascorbate-glutathione cycle and the NADP-dependent dehydrogenases located in these organelles.
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PMID:Cadmium toxicity and oxidative metabolism of pea leaf peroxisomes. 1069 37

In order to investigate the existence of genetic variability in antioxidant enzyme defenses in sunflower, twelve inbred lines, six cytoplasmic male-sterile and six restorer lines, commonly used in breeding programs have been compared with respect to (a) their levels of constitutive superoxide dismutase (SOD, EC 1.15.1.1), catalase (CAT, EC 1.11.1.6), ascorbate peroxidase (APX, EC 1.11.1.11), glutathione reductase (GR, EC 1.6.4.2) and guaiacol-dependent peroxidase (GPX, EC 1.11.1.7), and (b) their isoenzyme polymorphism in SOD, CAT, and GPX activities. Constitutive levels of antioxidant enzymes in the 2nd leaf pair of 15-20-day-old sunflower plants showed significant differences between lines. The ranges of variation in enzyme activities of the different lines were equivalent to 34.3% (CAT), 38.2% (SOD), 59.5% (APX), 60.0% (GR), and 62.9% (GPX) of the respective maximal values. Isoenzyme profiles of CAT, GPX and SOD revealed the existence in sunflower of at least three, six and four isoforms of these enzymes, respectively. Further characterization of SOD isoenzymes revealed that no isoenzyme corresponded to a Mn-SOD, the faster moving isoform being a Cu/Zn-SOD and the remainder three Fe-SODs. Among the twelve inbred sunflower lines studied there were ample qualitative, and sometimes quantitative too, differences in isoenzyme dotation of CAT, GPX and Fe-SOD.
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PMID:Sunflower (Helianthus annuus) variability in antioxidant enzyme defenses. 1069 64

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