Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30044 (antioxidant enzyme)
 8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitrogen dioxide (NO2), a major oxidant constituent of vehicle emissions, is toxic to lung cells including endothelial cells. Since NO2 is a reactive free radical, one of the postulated mechanisms of NO2-induced pulmonary injury involves the peroxidation of membrane lipids. Therefore, this study evaluated the dose- and time-dependent effects of nitrogen dioxide exposure by measuring the biochemical and biophysical parameters, as well as the metabolic function, in porcine pulmonary artery and aortic endothelial cells in monolayer cultures. To evaluate the biochemical changes, the antioxidant enzyme GSH-reductase (GSH-red), GSH-peroxidase (GSH-per), and glucose-6-phosphate dehydrogenase (G6PDH) activities, as well as the lipid peroxide formation, glutathione (GSH) content, and lactate dehydrogenase (LDH) release were measured. Biophysical changes were measured by monitoring lipid fluidity in both the hydrophobic and hydrophilic regions of the plasma membrane. The uptake of 5-hydroxytryptamine (5-HT) was measured as a metabolic function of endothelial cells. Confluent porcine pulmonary artery and aortic endothelial cells were exposed to 3 or 5 ppm NO2 or air (control) for 3-24 hours. After 3-, 6-, or 12-hour exposures to 3 or 5 ppm NO2, the GSH-red and G6PDH activities, as well as the lipid peroxide formation and LDH release, were not different from those of controls in both pulmonary artery and aortic endothelial cells. Exposure of the cells to 3 or 5 ppm NO2 for 24 hours resulted in significant increases in GSH-red (p less than 0.05) and G6PDH (p less than 0.001) activities in both cell types. Exposure to 5 ppm NO2 for 24 hours significantly (p less than 0.05) increased lipid peroxide formation and increased (p less than 0.01) LDH release in both the pulmonary artery and aortic endothelial cells. GSH-per activity and GSH content in NO2-exposed pulmonary artery and aortic endothelial cells were not different from those of controls, irrespective of NO2 concentration and exposure time. Fluorescence spectroscopy was used to measure the membrane lipid fluidity. Membrane fluidity in the hydrophobic region was measured by 1,6-diphenyl-1, 3, 5-hexatriene (DPH), an aromatic hydrocarbon that partitions into the hydrophobic interior of the lipid bilayer.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Biochemical and metabolic response to nitrogen dioxide-induced endothelial injury. 247 62

Disruption of cellular constituents including inhibition or "downregulation" of metabolic enzyme activity has been associated with free radical stress in locomotor muscle with acute, strenuous exercise. However, the effects of acute, strenuous exercise on important metabolic and antioxidant enzyme activity levels in the diaphragm are unknown. Twenty 4-month-old and twenty 24-month-old female Fischer-344 rats were divided at random into young exercised (YE; n = 10)/old exercised (OE; n = 10); young control (YC; n = 10)/old control (OC; n = 10) groups. Animals in both young and old exercise groups ran on a treadmill (10% uphill grade) for 40 min at approximately 75% of age group VO2 max. Immediately following the treadmill run, both exercise and control groups were euthanized with sodium pentobarbital. Costal (COD) and crural diaphragm (CRD) were quickly removed and frozen in liquid nitrogen. Lipid peroxidation was significantly increased (P < 0.05) in COD of YE vs. YC rats. Activity of the antioxidant enzyme glutathione peroxidase (GPX) was unaltered in the diaphragm by acute exercise (P > 0.05) in both age groups. There was a significant increase in superoxide dismutase (SOD) activity with exercise (P < 0.05). Post-hocs revealed SOD activity was approximately 20% greater (P = 0.066) in YE CRD only. Activities of the metabolic enzymes phosphofructokinase (PFK), succinate dehydrogenase (SDH), and citrate synthase (CS) were not affected by acute exercise in YE or OE. Strenuous exercise resulted in a small trend towards a decrease in 3-hydroxyacyl-CoA dehydrogenase (HADH) activity in YE COD (P = 0.115) and YE CRD (P = 0.082). We conclude that the employed bout of exercise induces some free radical stress, while metabolic enzymes are protected, in the diaphragm.
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PMID:Metabolic and antioxidant enzyme activities in the diaphragm: effects of acute exercise. 805 80

Intravenous administration of bacterial endotoxin (lipopolysaccharide: LPS) induces shock and disseminated intravascular coagulation in rats. Our report here shows that LPS-administered rats (10 mg/100 g) develop tissue injuries and functional disorders in multiple vital organs. In the present study, we investigated changes in tissue antioxidant enzyme activities, neutrophil sequestration, and lipid peroxides in multiple organs (lung, stomach, small intestine for antioxidant enzyme activities and neutrophil sequestration; lung, stomach, small intestine, liver, abdominal aorta for lipid peroxides) of LPS-treated rats. LPS-treated animals morphologically revealed pulmonary interstitial edema, alveolar hemorrhage, and mucosal hemorrhage in the small intestine 45 min after LPS administration. Blood samples withdrawn from LPS-treated animals exhibited increases in serum amylase, blood urea nitrogen, creatinine, and transaminase levels up to 180 min post-LPS infusion. LPS-treated animals showed a significant increase in tissue myeloperoxidase (MPO) activities of the lung, but not of the small intestine and stomach 45 min after LPS infusion. Thiobarbituric acid reactive substances (TBARS) in the lung, small intestine, stomach, liver, and abdominal aorta significantly increased at 45 min post-LPS-infusion. Tissue superoxide dismutase (SOD) activities of the LPS-treated animals demonstrated a significant decrease in the lung, which suffered from severe insults and neutrophil sequestration; no significant change in the small intestine, which suffered from morphological insults without neutrophil sequestration, and a significant increase in the stomach, which showed no histological impairment, at 180 min post-LPS administration. Glutathione peroxidase (GSH-PX) activities of the lung and small intestine showed no significant change in LPS-treated rats, while those of the stomach revealed a marked increase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in tissue antioxidant enzyme activities and lipid peroxides in endotoxin-induced multiple organ failure. 814 10

Changes in the integrity, ultrastructure, phagocytosis capacity, and production of H2O2, O2.- and NO2- were evaluated in cultured neutrophils. The activities of the antioxidant enzymes (catalase-CAT, superoxide dismutase-SOD and glutathione-dependent peroxidase-GSH-Px) were measured under similar conditions. The integrity of the cells remained unchanged up to 18 h. After 24 h, the number of viable cells in culture dropped by 16 per cent. The percentage of viable cells in culture was of 72 per cent even after 72 h. An ultrastructural analysis of the cells was carried out after 3, 6, 12, 24, 48, and 72 h in culture. Neutrophils started developing morphologic changes after 24 h: decreased cell volume, abundant vacuoles (mainly around the nucleus), and also the presence of autophagic vacuoles. This period was then chosen for the study of neutrophil function and antioxidant enzyme activities. Neutrophils cultured for 24 h presented reduced phagocytosis capacity. The rates of production of H2O2 and O2.- remained unchanged after 24 h in culture. Concomitantly, these cells were also able to produce NO in significant amounts. The production of O2.- in response to PMA stimulus was lowered in 24-h cultured cells. Possibly, the production of oxygen and nitrogen reactive species accomplished with a decrease in the activities of CAT and GSH-Px play a key role for the process of apoptosis which takes place in neutrophils under these conditions.
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PMID:Percentage of phagocytosis, production of O2.-, H2O2 and NO, and antioxidant enzyme activities of rat neutrophils in culture. 951 59

Copper-zinc superoxide dismutase (Cu,ZnSOD) is the antioxidant enzyme that catalyzes the dismutation of superoxide (O2*-) to O2 and H2O2. In addition, Cu,ZnSOD also exhibits peroxidase activity in the presence of H2O2, leading to self-inactivation and formation of a potent enzyme-bound oxidant. We report in this study that lipid peroxidation of L-alpha-lecithin liposomes was enhanced greatly during the SOD/H2O2 reaction in the presence of nitrite anion (NO2-) with or without the metal ion chelator, diethylenetriaminepentacetic acid. The presence of NO2- also greatly enhanced alpha-tocopherol (alpha-TH) oxidation by SOD/H2O2 in saturated 1, 2-dilauroyl-sn-glycero-3-phosphatidylcholine liposomes. The major product identified by HPLC and UV-studies was alpha-tocopheryl quinone. When 1,2-diauroyl-sn-glycero-3-phosphatidylcholine liposomes containing gamma-tocopherol (gamma-TH) were incubated with SOD/H2O2/NO2-, the major product identified was 5-NO2-gamma-TH. Nitrone spin traps significantly inhibited the formation of alpha-tocopheryl quinone and 5-NO2-gamma-TH. NO2- inhibited H2O2-dependent inactivation of SOD. A proposed mechanism of this protection involves the oxidation of NO2- by an SOD-bound oxidant to the nitrogen dioxide radical (*NO2). In this study, we have shown a new mechanism of nitration catalyzed by the peroxidase activity of SOD. We conclude that NO2- is a suitable probe for investigating the peroxidase activity of familial Amyotrophic Lateral Sclerosis-linked SOD mutants.
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PMID:Nitration of gamma-tocopherol and oxidation of alpha-tocopherol by copper-zinc superoxide dismutase/H2O2/NO2-: role of nitrogen dioxide free radical. 978 14

The effects of oxidative stress within post mitotic cells such as neurones may be cumulative, and injury by free radical species is a major potential cause of the age-related deterioration in neuronal function seen in several neurodegenerative diseases. There is strong evidence that oxidative stress plays an important role in the pathogenesis of motor neurone disease (MND). Point mutations in the antioxidant enzyme Cu,Zn superoxide dismutase (SOD1) are found in some pedigrees with the familial form of MND. How mutations in this ubiquitous enzyme cause the relatively selective cell death of specific groups of motor neurones is not clear, although a number of hypotheses have been forwarded. These include (1) the formation of hydroxyl radicals, (2) the catalysis of reactions of the nitrogen centred oxidant species peroxynitrite, (3) toxicity of copper or zinc and (4) protein aggregation. Some experimental support for these different hypotheses has been produced by manipulating cells in culture to express the mutant SOD1 proteins and by generating transgenic mice which over-express mutant SOD1. Observations in these model systems are, in some cases at least, supported by observations made on pathological material from patients with similar SOD1 mutations. Furthermore, there are reports of evidence of free radical mediated damage to neurones in the sporadic form of MND. Several lines of evidence suggest that alterations in the glutamatergic neurotransmitter system may also play a key role in the injury to motor neurones in sporadic MND. There are several important subcellular targets, which may be preferentially impaired within motor neurones, including neurofilament proteins and mitochondria. Future research will need to identify the aspects of the molecular and physiological phenotype of human motor neurones that makes them susceptible to degeneration in MND, and to identify those genetic and environmental factors which combine to cause this disease in individuals and in familial pedigrees.
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PMID:Oxidative stress and motor neurone disease. 998 58

The long-term effect of limiting soil nitrogen (N) availability on foliar antioxidants, thermal energy dissipation, photosynthetic and respiratory electron transport, and carbohydrates was investigated in Spinacia oleracea L. Starch, sucrose, and glucose accumulated in leaves of N-limited spinach at predawn, consistent with a downregulation of chloroplast processes by whole-plant sink limitation in response to a limited supply of N-based macromolecules throughout the plant. On a leaf-area or dry-weight basis, levels of chlorophyll, carotenoid pools, photosynthetic electron transport capacity, as well as activities for the predominantly chloroplast-localized antioxidant enzymes ascorbate peroxidase (EC 1.11.1.11) and glutathione reductase (EC 1.6.4.2) were much lower in N-limited versus N-replete plants. When expressed on a chlorophyll basis, foliar levels of all of these parameters were similar in N-replete versus N-limited plants. However, on a total-protein basis, antioxidant enzyme activities were higher in N-limited plants. Nitrogen-limited spinach showed higher levels of thermal energy dissipation and of zeaxanthin and antheraxanthin at midday, as well as slightly higher ascorbate contents relative to chlorophyll. These results indicate that strong, long-term N limitation led not only to alterations in the balance between different processes but also to an overall downregulation of light collection, photosynthetic electron transport capacity, and chloroplast-based antioxidant enzymes. This is further supported by the finding that glucose-feeding of excised leaves led to strong concomitant decreases in photosynthetic electron transport capacity and ascorbate peroxidase activity. On a leaf-area basis, neither superoxide dismutase (EC 1.15.1.1) activity nor dark repiration rates showed a treatment effect. This indicates that overall mitochondrial electron transport activity does not decrease under long-term N limitation and is consistent with localization of an important fraction of foliar superoxide dismutase in mitochondria.
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PMID:Effect of nitrogen limitation on foliar antioxidants in relationship to other metabolic characteristics. 1043 24

Free radicals are thought to be the most important cause of the reperfusion injury subsequent to ischemia. The antioxidant status of the tissue affected by ischemia-reperfusion is of great importance for the primary endogenous defense against the free radical induced injury. This investigation was performed to evaluate the antioxidant enzyme capacity of the brain tissue in the ischemia-reperfusion period using an experimental global moderate (penumbral) ischemia model on rat brains. Experiments were performed on 45 male Sprague Dawley rats. Ischemia was induced by bilateral vertebral arteries cauterization and temporary bilateral carotid arteries occlusion and sustained for 10 minutes. At the end of ischemia (0 min reperfusion) and various reperfusion periods (20 min, 60 min, 240 min), rats were decapitated and brains were frozen in liquid nitrogen. Changes in the intracellular antioxidant enzyme (superoxide dismutase, glutathione peroxidase and catalase) activities were assessed in the rat brain tissues, by spectrophotometric methods. In all moderate ischemia-reperfusion groups, superoxide dismutase activities were found to have decreased significantly compared to the sham operated controls (P < 0.05). During ischemia superoxide dismutase activity was lowered to 31% of that of the control group. The decreases were more significant in reperfusion groups, particularly in 60 min reperfusion (40%). Relatively smaller but still significant diminution was observed in glutathione peroxidase activities (P < 0.05). The ratio of diminution was striking in 20 min and 60 min reperfusion groups with 26% of the sham operated rats. Conversely, moderate ischemia-reperfusion caused significant increase in catalase activities (P < 0.05). The increment was 63% of the preischemic level with 10 min of moderate ischemia. In conclusion, activities of the major antioxidant enzymes were changed significantly in moderate brain ischemia-reperfusion. These results suggest that the disturbance in oxidant-antioxidant balance might play a part in rendering the tissue more vulnerable to free radical induced injuries.
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PMID:Alterations in superoxide dismutase, glutathione peroxidase and catalase activities in experimental cerebral ischemia-reperfusion. 1063

To investigate the effects of repeated exposure to nitrogen dioxide (NO2) on antioxidant enzymes in lung tissue and isolated lung cells, rats were continuously exposed to 20 mg/m3 NO2 (10.6 ppm) for 4 days. The activities of glucose-6-phosphate dehydrogenase (G6PDH), glutathione reductase (GR), and glutathione peroxidase (GSHPx) were measured in the cytosolic fraction of lung tissue of both control and NO2-exposed rats as well as in isolated alveolar macrophages (AMs) and type II cells. Qualitative and quantitative changes in AM and type II cells were studied by electron microscopy and by morphometric analyses using enzyme and immunohistochemistry. NO2 exposure resulted in significantly increased pulmonary activities of G6PDH, GR, and GSHPx, both expressed per lung and per gram of lung weight. Morphometric data show that NO2 exposure significantly increased the number of type II cells, predominantly in the centriacinar region, indicating proliferation of epithelium following cellular injury. Type II cells in lungs of NO2-exposed rats had a squamous, less cuboidal appearance with more lamellar bodies compared to type II cells in lungs of control rats. Compared to control lungs, a higher number of macrophages could be isolated from NO2-exposed lungs, while numbers of type II cells isolated from lungs of control and NO2-exposed rats were the same. Isolated type II cells from control and NO2-exposed rats were polymorphic, with a small number of lamellar bodies and without polarity. Isolated macrophages were rounded and contained many filopodia. NO2 exposure caused increases in the activities of G6PDH and GSHPx in isolated type II cells and of GSHPx in isolated macrophages, when expressed per number of cells. Macrophages and type II cells isolated from control and NO2-exposed rats and re-exposed in vitro to NO2, showed no differences in phagocytosis and viability features. Our results indicate that NO2-induced increases in pulmonary antioxidant enzymes are also reflected in isolated AM and type II cells. Since these lung cells do not display a decreased sensitivities toward an in vitro NO2 exposure, overall increase in antioxidant enzyme activities do not seem to play the most pivotal role in controlling cellular NO2 sensitivity and oxidant defence. Combined data from biochemical, morphological, and morphometric analyses of lungs and lung cells suggest that lung cell and tissue oxidant sensitivity and defence largely depends on the cell and tissue organisation, i.e., cell numbers and morphology as well as the ratio of surface area to cytoplasmic volume.
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PMID:Biochemical and morphological changes in lung tissue and isolated lung cells of rats induced by short-term nitrogen dioxide exposure. 1100 89

The ability of ebselen, which exhibits glutathione peroxidase (GSH-Px)-like activity, to prevent cisplatin (CDDP)-induced nephrotoxicity was examined in rats. CDDP (6 mg/kg [20 micromol/kg] body weight) was injected intraperitoneally. In subgroups, daily ebselen doses of 2.75 (10 micromol), 5.5 (20 micromol), or 11.0 mg (40 micromol)/kg body weight were administrated orally 1 hour prior to CDDP treatment. Treatment with CDDP alone resulted in significantly increased plasma creatinine (Cr) and blood urea nitrogen (BUN) levels. Repeated administration of 5.5 and 11.0 mg/kg ebselen prevented the CDDP-induced elevation of plasma Cr and BUN levels and protected against kidney damage. Relative to controls, rat that received CDDP treatment displayed a decreased ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG), an indicator directly related to oxidative stress, and elevated malondialdehyde (MDA) levels in the kidney. In comparison with controls, activity of GSH-Px activity, which antioxidant enzyme, was also reduced in the kidney of rats treated with CDDP. Repeated administration of 5.5 or 11.0 mg/kg ebselen prevented CDDP-induced alteration of GSH/GSSG ratios, MDA levels, and GSH-Px activity; however, no protection against CDDP was observed with administration of 2.75 mg/kg ebselen. Effective protection of CDDP-induced nephrotoxicity with ebselen was observed only when the molar amount of each daily ebselen treatment equaled or exceeded
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PMID:Prevention of nephrotoxicity of cisplatin by repeated oral administration of ebselen in rats. 1103 13


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