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 intracellular steady-state concentrations of hydrogen peroxide or superoxide anion were increased by inhibiting either catalase, glutathione peroxidase, or superoxide dismutase activities. Catalase was inhibited with aminotriazole while glutathione peroxidase activity was blocked by eliminating reduced glutathione after addition of either iodoacetamide diethylmaleate or phorone. The concentration of aminotriazole that stimulated chemiluminescence in 50% (60 mM) was very similar to the Ki for catalase activity (70 mM). Cyanide, an inhibitor of both catalase and superoxide dismutase, stimulated chemiluminescence in 50% at a concentration (0.15 mM) which is much closer from the Ki for superoxide dismutase (0.25 mM) than from the Ki for catalase (15 microM). The superoxide dismutase inhibitor diethyldithiocarbamate also increased chemiluminescence six- to ten-fold. Depletion of reduced glutathione stimulated spontaneous chemiluminescence when its concentration decreased below 4.5 mumol X g liver-1. The results shown herein suggest that the changes in the intracellular steady-state concentration occurring after inhibition of any antioxidant enzyme are responsible for the increased spontaneous chemiluminescence. Spontaneous chemiluminescence from intact cells may be used as a noninvasive method for monitoring intracellular free radical metabolism.
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PMID:Increased spontaneous chemiluminescence from liver homogenates and isolated hepatocytes upon inhibition of O2- and H2O2 utilization. 302 9

Relative cell survival and activity of the free radical scavenging enzymes superoxide dismutase, catalase, and glutathione peroxidase were measured in cloned normal (MEA) and SV40-transformed (SVMEA) mouse embryo cells exposed at 44 degrees C for 0-3 h. At 37 degrees C, all three enzymes were 2-5 times higher in MEA than in SVMEA. Hyperthermia did not significantly alter enzyme levels in either cell line but selectively reduced transformed cell survival to less than 5% while relative survival of normal cells remained above 75%. The latter, however, could be reduced to 25% when normal cells were pretreated with 3 mM diethyldithiocarbamate, an inhibitor of copper- and zinc-containing superoxide dismutase. Similar treatment rendered SVMEA extremely thermosensitive. On the other hand, sublethal heat treatment (15 min at 45 degrees C) of cultured cells resulted in a relative thermal resistance upon subsequent exposure to 45 degrees C for 1-4 h. This induced thermotolerance was associated with a rise in antioxidant enzyme levels and both became significant only 4-6 h after the initial heat treatment. Induced enzyme and thermotolerance levels in transformed cells remained, nonetheless, far below those of normal cells. The data show that inherent (in MEA) as well as induced (in SVMEA) thermotolerance is associated with high antioxidant enzyme levels while the reverse is true in the case of inherent (in SVMEA) and induced (in MEA) thermosensitivity. These findings suggest that increased production of oxygen free radicals may be involved in hyperthermic cell injury, which then becomes a function of basal or inducible levels of antioxidant enzymes. Induction of the latter by hyperthermia is apparently inefficient in transformed cells making them more vulnerable. Enzyme induction seems also to require a lag period of 4-6 h suggesting the possible involvement of an intermediate inducer(s) at molecular level. The so-called heat shock proteins may be candidates for such a role.
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PMID:Antioxidant enzymes and survival of normal and simian virus 40-transformed mouse embryo cells after hyperthermia. 303 17

The failure of adult rats to survive prolonged exposure to greater than 95% O2 is generally ascribed to the inability of their lungs to increase antioxidant enzyme synthesis in response to the oxidant challenge. We studied the synthesis rate of the antioxidant enzyme CuZn superoxide dismutase (CuZn SOD) in lungs of adult and neonatal rats exposed to conditions that alter the lung's oxidant-to-antioxidant balance. Lung CuZn SOD synthesis in the adult was significantly increased after 24 h of hyperoxia but fell to control levels after further exposure, whereas in neonatal lungs an increased rate of synthesis of CuZn SOD was found only after 72 h of hyperoxia. The adult lung responded to two in vitro oxidant stresses, [diethyldithiocarbamate exposure and heat (42 degrees C)] with increases in CuZn SOD synthesis twice the magnitude of those in the neonatal lung. These data indicate that the adult lung is at least as capable as the neonatal lung of increasing its synthesis of CuZn SOD in response to an oxidative stress. However, the inability of the adult lung to maintain an increased rate of CuZn SOD synthesis during in vivo hyperoxia may contribute to the poor tolerance of the adult lung to greater than 95% O2.
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PMID:Differences in CuZn superoxide dismutase induction in lungs of neonatal and adult rats. 303 15

Preexposure of rats to sublethal levels of hyperoxia or ozone reduces morbidity and mortality when the animals are subsequently exposed to lethal levels of either oxidant stress. Lung homogenates and isolated type II pneumocytes from rats exposed to these oxidant stresses demonstrate enhanced antioxidant enzyme activities. Antioxidant enzymes, superoxide dismutase, catalase, and glutathione peroxidase are responsible for the detoxification of partially reduced oxygen species, superoxide and hydrogen peroxide, to less reactive states. Potential pulmonary cellular loci of partially reduced oxygen include mitochondrial NADH dehydrogenase, endoplasmic reticulum-derived NADPH cytochrome c reductase, and cytosolic xanthine oxido reductase. Thus partially reduced oxygen species are hypothesized to mediate hyperoxia and ozone-induced pulmonary damage. This damage may be attenuated by enhanced intracellular antioxidant enzyme activities. Pharmacologic augmentation of pulmonary antioxidant enzymes may be accomplished via intratracheal or intravascular delivery of liposomes containing antioxidant enzymes. Rats pretreated with liposomes containing both superoxide dismutase and catalase, when subsequently exposed to lethal levels of hyperoxia, demonstrate enhanced survival compared with control animals or with animals treated with control liposomes or native antioxidant enzymes. Finally, knowledge obtained from in vitro investigations optimizing liposomal delivery to specific pulmonary cell types may further aid in reducing in vivo pulmonary damage to hyperoxia and ozone.
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PMID:Pulmonary metabolism of reactive oxygen species. 306 93

Increasing evidence suggests a role for reactive free radical oxygen species in the multi-stage events of chemical carcinogenesis. We hypothesized that variations in the level of superoxide dismutase (SOD), a major endogenous antioxidant enzyme, may account in part for variations in susceptibility to cancer induced by polycyclic aromatic hydrocarbons (PAH). The SOD activity of mammary epithelial cells from rats with varying susceptibility to dimethylbenz[a]anthracene (DMBA)-induced breast cancer was assayed. Ageing, pregnancy and previous multiple pregnancies reduce susceptibility of Sprague--Dawley female rats to DMBA. These decreases in susceptibility were correlated with increased levels of SOD activity. Only minor differences in SOD activity was observed in mammary epithelium of genetic strains of rats with differences in susceptibility to DMBA. These data suggest that, in models where physiological differences may account for variations in effectiveness of PAH to induce mammary cancer, SOD activity is inversely correlated with breast cancer susceptibility and support the hypothesis that cancer susceptibility may be partially mediated through reactive free radical oxygen intermediates.
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PMID:Relationships between cellular superoxide dismutase and susceptibility to chemically induced cancer in the rat mammary gland. 308 49

Serum levels of the trace metals copper, zinc, and selenium were measured in premature infants. White blood cell glutathione peroxidase and superoxide dismutase levels were measured in conjunction with the trace metals. Three groups of infants were evaluated: group I was relatively healthy, group II were infants with stage 2 bronchopulmonary dysplasia (BPD) or less, group III were infants with stage 3 BPD or worse. Zinc and selenium levels declined in all groups during conventional parenteral nutrition (TPN) regimens, while copper remained stable. Copper did decline in groups I and II coincident with an acceleration in growth rate. An expected rise in antioxidant enzyme levels in infants with pulmonary oxygen toxicity was not seen. This study suggests that supplemental selenium as well as an increased zinc intake over current recommendations for premature infants receiving TPN may be indicated.
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PMID:Relationship of antioxidant enzymes to trace metals in premature infants. 310 37

Oxygen free radicals have the potential to mediate cell injury. Defenses against such radicals include the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX). The purposes of this study were (1) to develop an in vitro model using human cells in which to investigate a potential pharmacologic agent as an inducer of these antioxidant enzymes; (2) to investigate the phenylurea derivative N-[2-(2-oxo-1-imidazolindinyl)ethyl]-N-phenylurea (EDU) in this model with paraquat (PQ) serving as the positive control; and (3) to determine if induction of the antioxidant enzymes by EDU occurs in vivo. Human gingival fibroblasts (Gin-1) were used as the target cell in vitro; PQ and EDU, an inducer of SOD and CAT activities in plants, were evaluated as antioxidant enzyme inducers. Total SOD activity in Gin-1 cells increased 2-fold (p less than 0.05) in the presence of 1.0 mM PQ for 18-48 hr compared with untreated controls. Gin-1 cells incubated with 0.25-2.0 mM PQ for 24 hr had significantly increased total SOD (1.5 to 2.0-fold; p less than 0.05). CAT activity increased with 1.0 and 2.0 mM PQ (p less than 0.05). In the presence of PQ, GSH-PX activity decreased (p less than 0.05) in a concentration-dependent manner, indicating inactivation of this enzyme. No toxicity, indicated by lactate dehydrogenase released into the incubation medium, was noted at PQ concentrations below 5.0 mM. In the presence of 0.125-2.0 mM EDU, total SOD activity in Gin-1 cells significantly increased (1.5 to 2.0-fold; p less than 0.05). CAT activity significantly increased in a dose-dependent manner (p less than 0.05), while GSH-PX activity remained constant following exposure to 0.125-2.0 mM EDU. Intraperitoneal administration of EDU to rats twice a day for 2 days at 100 mg/kg induced SOD activity in heart, liver, and lung compared to controls (p less than 0.05). CAT activity increased in the liver 56% and in the lung 36% (p less than 0.05). GSH-PX activity remained constant. Our findings indicate that Gin-1 cells are a useful model in which to study inducers of antioxidant enzymes in vitro and that the phenylurea compound EDU induces SOD and CAT activities both in vitro and in vivo.
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PMID:Induction of antioxidant enzyme activities by a phenylurea derivative, EDU. 318 24

A study was made of the changes in the activities of the antioxidant enzymes superoxide dismutase and catalase in the blood of chronic uraemic patients before and after haemodialysis. Changes in serum lipids (primarily neutral lipids), lipoproteins and lipid peroxidation were also followed. Before haemodialysis, antioxidant enzyme activities decreased, while lipid peroxidation increased both in the plasma and in the RBC haemolysates. Quantitative changes in the lipids increased the risk factors. Haemodialysis moderated these risk factors and a tendency to improvement was observed.
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PMID:Changes and correlations of antioxidant enzymes, lipid peroxidation and serum neutral lipids due to haemodialysis treatment in chronic uraemic patients. 323 7

The effect of copper deficiency on blood cholesterol and antioxidant defense mechanisms was investigated in male and female rats. Diets low in copper (Cu, 0.3 mg/kg) were given to a group of male (n = 5) and a group of female (n = 5), weanling Wistar rats for ten weeks. Diets containing adequate copper (Cu, 3.7 mg/kg) fed to another group of males (n = 5) and another group of females (n = 5) served as controls. Serum cholesterol levels and erythrocyte, granulocyte, lymphocyte and macrophage antioxidant enzyme activities were compared. Only copper deficient males showed increased serum cholesterol levels compared to controls. There were no significantly differences in erythrocyte measurements due to copper status, but males had significantly (P less than 0.05) higher haemoglobin levels, and erythrocyte catalase (CAT) and superoxide dismutase (SOD) activities than females. Low copper diets significantly decreased granulocyte SOD (P less than 0.01) in males, peritoneal macrophage SOD in females and lymphocyte SOD (P less than 0.05) in both sexes. Female controls had significantly (P less than 0.01) higher macrophage SOD than male controls and lymphocyte SOD was significantly higher in females. Results demonstrate sex differentiated effects of low copper diets on blood cholesterol and antioxidant defence mechanisms.
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PMID:The effect of a low copper diet on blood cholesterol and enzymic antioxidant defense mechanisms in male and female rats. 324 99

Analyses were made of the phsopholipid fatty acids and the antioxidant enzymes in the carp (Cyprinus carpio morpha) at three different oxygen concentrations, corresponding to hyperoxia, hypoxia and anoxia. Variations of the oxygen concentration were found to influence the quantities of phsopholipid fatty acids, as well as the antioxidant enzyme activities. In hyperoxia and hypoxia the amount of polyunsaturated fatty acids in carp liver was higher than in anoxia, but in other tissues there was no significant differences. As to the antioxidant enzyme system, the glutathione peroxidase activity and the lipid peroxidation value increased significantly with decrease of the oxygen concentration, while the total superoxide dismutase activity decreased on lowering of the oxygen level.
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PMID:Effects of various oxygen concentrations on antioxidant enzymes and the quantity of tissue phospholipid fatty acids in the carp. 325 9


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