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)

The toxicity of the antineoplastic agent doxorubicin (DOX) has been shown to be moderated by the antioxidant enzyme glutathione peroxidase. It has been reported that acute doses of DOX can cause an inhibition of glutathione peroxidase in cardiac tissue, that may render this tissue especially susceptible to further prooxidant damage. In this study, multiple DOX treatments at a therapeutic dose were assessed for their effect on the antioxidant enzyme status of cardiac and kidney tissue. DOX was administered i.p. (5 mg/kg) once a week for two weeks to male balb/c mice. The activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPOX) and glutathione reductase (GR) were measured 1, 2 and 7 days following the second DOX treatment in both heart and kidney. Levels of reduced glutathione (GSH) were also measured in cardiac tissue at these same times. Cardiac levels of GPOX and GR showed a time-dependent decrease in activity, with 10% and 12% inhibition for GPOX and GR, respectively, at 7 days post second treatment. Cardiac levels of GSH also showed a significant decrease, approximately 15%, at 7 days post second treatment. Cardiac levels of SOD and CAT as well as kidney levels of all four antioxidant enzymes were not affected by DOX treatment. These data suggest that DOX given in a therapeutic regimen, at a therapeutic dose, can cause decreases in cardiac levels of GPOX, GR and GSH that could render the heart especially susceptible to further oxidative challenge.
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PMID:Modulation of glutathione and glutathione dependent antioxidant enzymes in mouse heart following doxorubicin therapy. 822 37

Feeding diets depleted of vitamin E and Se to cattle can induce a disease known as nutritional degenerative myopathy. It is believed that an increased peroxidative challenge in muscle is involved in the pathogenesis of this disease. A number of species can up-regulate the activity of some antioxidant enzymes, including glutathione reductase (EC 1.6.4.2), glutathione transferase (EC 2.5.1.18), glucose-6-phosphate dehydrogenase (EC 1.1.1.49), catalase (EC 1.11.1.6), and superoxide dismutase (EC 1.15.1.1), in an attempt to mitigate the effects of a peroxidative challenge. A 2 x 2 factorial study was set up to examine possible changes in the activities of these antioxidant enzymes in muscles of ruminant calves fed on diets low in either vitamin E or Se. Four groups of four calves each were fed on a basal diet of NaOH-treated barley which was supplemented with alpha-tocopherol or Se or both for a total of 50 weeks. Calves fed on diets depleted of vitamin E, but not those fed on diets low in Se, developed subclinical myopathy, as judged by increases in the activity of plasma creatinine kinase (EC 2.7.3.2), and had increased muscle concentrations of two indices of lipid peroxidation, namely thiobarbituric acid-reactive substances, with and without ascorbate activation. Feeding diets depleted of vitamin E and diets low in Se both increased muscle activities of glucose-6-phosphate dehydrogenase in heart, biceps and supraspinatus. This change may have occurred in an attempt to maintain intracellular pools of reduced glutathione. No other changes in antioxidant enzyme activity were observed.
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PMID:Antioxidant enzyme activity in the muscles of calves depleted of vitamin E or selenium or both. 826 Apr 86

Normal embryonal mouse liver cells in culture were shown to undergo spontaneous transformation during prolonged subculture. The spontaneously transformed cells lost their anchorage dependence, as measured by a soft agar assay, and gave rise to tumors in nude mice. Accompanying this transformation, the antioxidant enzymes, copper- and zinc-containing superoxide dismutase (CuZnSOD), manganese superoxide dismutase (MnSOD), catalase (CAT) and glutathione reductase, decreased significantly in activity; the decline in enzymatic activity of CuZnSOD, MnSOD and CAT was due to a decline in the levels of immunoreactive protein. These spontaneously transformed high passage in vitro liver cells appeared similar in morphology, antioxidant enzyme activity and tumorigenicity to their counterparts transformed by N-methyl-N-nitro-N-nitrosoguanidine and Simian virus 40. These data provide experimental evidence that changes in antioxidant enzymes are associated with spontaneous in vitro cellular transformation of mouse embryonal liver cells.
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PMID:Lowered antioxidant enzymes in spontaneously transformed embryonic mouse liver cells in culture. 833 Mar 64

This study examined whether brief repeated myocardial ischemia altered free radical generating and scavenging activity in a dog model. In dogs preconditioned with four 5-min left anterior descending coronary artery (LAD) occlusions and reperfusions, we examined transcardiac changes in both the function of neutrophils, cells which are major free radical generators, and in myocardial antioxidant enzyme activity, as an indication of free radical scavenging. Neutrophil function was assessed by determining luminol-enhanced whole blood chemiluminescence (CL) induced by zymosan. Blood was taken simultaneously from the carotid artery and the cardiac vein running along the occluded LAD. Preconditioning with sublethal ischemia significantly reduced whole blood CL in the cardiac vein compared with the carotid artery after the first and fourth 5-min reperfusions, while there was no difference in neutrophil count between these sampling sites. Immediately after brief repeated ischemia and reperfusion, manganese-superoxide dismutase (SOD) activity was significantly enhanced, and glutathione reductase activity was markedly reduced in the ischemic, compared with the non-ischemic, myocardium. There were no differences in the myocardial activities of copper, zinc-SOD, glutathione peroxidase, and glutathione S-transferase between the ischemic and non-ischemic regions. Also, no difference was observed between the reduced myocardial glutathione levels in these regions, although the oxidized glutathione level was significantly higher in the ischemic regions of the subepicardial and subendocardial areas. We demonstrated that brief repeated ischemia affects free radical generating and scavenging systems in the ischemic myocardium.
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PMID:Brief myocardial ischemia affects free radical generating and scavenging systems in dogs. 840 20

To clarify the mechanism of oxidative stress in skeletal muscle atrophied by immobilization, we investigated the change of antioxidant enzyme activities in a typical slow red muscle, the soleus. Atrophied soleus muscles were collected from male Wistar rats (16 weeks old), one ankle joint of which had been immobilized in the fully extended position for 7 days. Also, soleus muscles were collected from intact age-matched rats as control. The activities of Mn-containing superoxide dismutase (Mn-SOD), Cu,Zn-containing superoxide dismutase (Cu,Zn-SOD), Se-dependent glutathione peroxidase (Se-GSHPx), glutathione S-transferase (GST), catalase, and glutathione reductase (GSSGRx) were measured. The activities of Cu,Zn-SOD, GST, and GSSGRx were significantly higher in atrophied muscles, while the others were unchanged. Increased Cu,Zn-SOD and unchanged Mn-SOD levels might reflect increased generation of superoxide anions in the cytoplasm rather than in the mitochondria. Owing to the enhancement of Cu,Zn-SOD and the unaltered Se-GSHPx and catalase activities, hydrogen peroxide is thought to be increased in the cytoplasm. Because there is also an increase of iron in the microsomes of atrophied muscles, the production of hydroxyl radicals, the most aggressive of radicals, might consequently be elevated.
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PMID:Antioxidant enzyme systems in skeletal muscle atrophied by immobilization. 843 91

Insulin-dependent diabetes (IDD) in the nonobese diabetic (NOD) mouse is believed to result from the specific autoimmune destruction of pancreatic beta cells. The frequency of diabetes in the NOD mouse is sex-dependent, with approximately 90% of females and 40% of males developing clinical diabetes by 40 weeks of age. Recently, attention has focused on determining possible mechanisms for beta cell destruction. One potential mechanism is the toxic effect of free oxygen radicals produced as a result of the influx of inflammatory cells into the pancreas. A deficiency in available antioxidant enzymes could form a basis for diabetes susceptibility. To test the feasibility of this idea, we have compared the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase in isolated islets, pancreas, and other tissues of age- and sex-matched NOD, BALB/c, C57BL/10, and B10.GD mice. Enzyme profiles revealed that female NOD mice do not differ significantly in antioxidant enzyme activity from females of the other inbred strains. However, antioxidant enzyme activity in females was generally lower than in males regardless of mouse strain. While isolated islet cells exhibited somewhat lower levels of enzyme activity than other tissues, the islets of NOD mice proved to be no more deficient than those of BALB/c mice. Therefore, it is unlikely that any toxic effect of free oxygen radicals on the beta cells of NOD mice results directly or solely from an antioxidant enzyme deficiency. Nevertheless, one possible explanation for the lower incidence of diabetes in NOD males versus females may be the inherently higher male antioxidant enzyme activities.
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PMID:Antioxidant enzyme activities in IDD-prone and IDD-resistant mice: a comparative study. 846 25

The effects of intracellularly generated H2O2 on cell viability, morphology, and biochemical markers of injury have been investigated in a clonal cell line of neuronal origin (140-3, mouse neuroblastoma X rat glioma) as a cell culture model for the role of oxidative stress in the long-term loss of neurons in the brain. The H2O2 was generated from the redox cycling of menadione, or by the oxidation of serotonin catalyzed by monoamine oxidase, to simulate the effect of amine neurotransmitter turnover. Incubation with menadione at concentrations as low as 10 microM for several hours resulted in significant losses of cell viability and altered morphology. Similar effects were evident in the presence of serotonin only after incubation overnight with concentrations > 1 mM. The cytotoxicity of either agent was potentiated by preincubation with specific inhibitors of two enzymes important to cellular antioxidant defenses, 3-amino-1,2,4-triazole for catalase and 1,3-bis(chloromethyl)-1-nitrosourea for glutathione reductase. Activity of another antioxidant enzyme of particular importance to antioxidant defenses in brain, the selenoprotein glutathione peroxidase, was stimulated fourfold by growth of cultures in the presence of sodium selenite as a source of active-site Se for the enzyme. The only effect of the selenite on other functionally coupled antioxidant enzymes was a decrease in activity of superoxide dismutase at concentrations > 200 nM. The selenite substantially protected cells against oxidative stress induced by combinations of menadione, 3-amino-1,2,4-triazole, and 1,3-bis(chloromethyl)-1-nitrosourea, but was only marginally effective with serotonin as a source of oxidative stress. The monoamine oxidase inhibitor pargyline increased cell survival in the presence of serotonin, demonstrating the role of this enzyme in its cytotoxicity. DNA damage (single strand breaks), but not lipid peroxidation, correlated with the cytotoxic effects of menadione.
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PMID:Oxidative stress in a clonal cell line of neuronal origin: effects of antioxidant enzyme modulation. 849 17

We used several biochemical assays to evaluate age-related changes in antioxidant enzyme levels vs. free-radical damage in the murine brain. We found levels of several free-radical scavenging enzymes in the brains of 24-month-old C57B1 male mice vs. 12-month-old animals were decreased, including superoxide dismutase (SOD), catalase, and glutathione reductase (GSSG-Rd). In addition, we found concomitant increases in the levels of several forms of free-radical damage including sensitivity to lipid peroxidation as measured by the thiobarbituric acid test, protein oxidation as measured by glutamine synthetase (Gln Syn) activity, as well as increases in oxidized glutathione (GSSG) levels, a measure of oxidative stress. These data suggest that decreases in levels of enzymes which ordinarily protect neuronal cells against oxidative stress with age may be responsible for increased levels of free-radical damage in the murine brain, or that these enzymes themselves are susceptible to inactivation by free radical molecules which increase with age in the brain.
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PMID:Decreases in protective enzymes correlates with increased oxidative damage in the aging mouse brain. 856 82

Enzymatic and non-enzymatic antioxidant profiles of the gastric and duodenal mucosa of rat, rabbit, cat and pig were investigated and found to exhibit significant variations. Rat gastric and duodenal mucosa exhibited the highest levels of basal glutathione of the various tissues examined. The highest activity of glutathione reductase was found in the gastric and duodenal mucosa of rat as compared with that in these tissues from the other species. The gastric mucosa of cat and pig showed similar activities of glutathione peroxidase, which was significantly lower than those in rat or rabbit gastric mucosa. The activity of this antioxidant enzyme was similar in rat, rabbit and pig duodenal mucosa and lower than that in cat duodenal mucosa. Strong correlations were found between activities of the functionally coupled antioxidant enzymes glutathione peroxidase and glutathione reductase in gastric but not in duodenal mucosa. The activity of superoxide dismutase showed negligible regional or species-related variations in activity.
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PMID:Species-related variations in antioxidant components of gastric and duodenal mucosa. 859 Mar 84

The purpose of this research was to evaluate the effect of age on protective antioxidant enzyme activity of normal fresh cadaver human retina of the macula and periphery. Antioxidant enzymes were assayed in tissue extracts generated from 5 mm trephined punches of retina obtained centered over the macula and the superior midperiphery of normal fresh human cadaver retina. Cadaver tissue was obtained from donors of a wide age range (age 7 to 85 years). The assays were performed within 6 h of enucleation and within 24 h of donor death. Antioxidant enzymes assayed included superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. Hexokinase and glucose-6-phosphate dehydrogenase, enzymes not directly involved in protection against oxidative damage, were assayed for comparison. Enzyme specific activities were calculated for the macula and periphery using protein concentration of the extract as the denominator. Using linear regression analysis, over the age range of 25 to 75 years, superoxide dismutase activity of the periphery but not the macula tended to decline with age (p = 0.04, R2 = 0.21). Interindividual variability was high, and variability increased with age. The difference between the macular and peripheral enzyme activities for glutathione peroxidase tended to decline with increasing donor age (p = 0.025, R2 = 0.33). There was no effect of age on the specific activities of catalase, glucose-6-phosphate dehydrogenase, and glutathione reductase. The specific activity of hexokinase from the macula declined with increasing donor age (p = 0.022, R2 = 0.43). Time from death to enucleation or beginning of experiment was not a significant factor. In summary, age does not have an effect on the activity of major antioxidant enzymes of the macula in normal human retina. There is a tendency for an effect of age on peripheral superoxide dismutase activity and the difference between macular and peripheral glutathione peroxidase activity. High interindividual variability of antioxidant enzyme activity exists in humans.
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PMID:Antioxidant enzymes of the human retina: effect of age on enzyme activity of macula and periphery. 865 7


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