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)

Supplements of antioxidants, superoxide dismutase (SOD), catalase, cyclic guanylate (cGMP), and theophylline, or omission of iron and copper from the medium are therapeutic for the inferior growth and viability of yeast mutants doubly deficient in mitochondrial and exocellular SOD isozymes under oxidative stresses. Cyclic adenylate tends to be ineffective or counterproductive. Oxy-stress resistant revertants are cross-resistant to other oxy-stresses and acquire one, the other, or both isozymes. The principal conclusions are: i) a genetic defect in cGMP metabolism probably compromises regulation of the enzymes' synthesis; ii) the enzymes are only essential for growth and viability under oxidative stresses; iii) oxidative toxicity is mediated by both exo- and endocellular oxy-radicals, particularly hydroxyl radicals; and iv) the pharmacogenetic features and the mutants' phenotypes are quite similar to those of negative antioxidant enzyme regulatory mutants of the related ascomycete Neurospora.
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PMID:Pharmacogenetics of cyclic guanylate, antioxidants, and antioxidant enzymes in Saccharomyces. 217 Feb 45

The human hepatoma cell line Hep 3B, which has the hepatitis B virus genome, shows over 80% decrease of copper/zinc superoxide dismutase activity, over 90% decrease of manganese superoxide dismutase activity, over 70% decrease of catalase activity, absence of glutathione peroxidase and glutathione S-transferase activities, over 270-fold increase of ferritin content and 25-fold increase of total iron compared to normal autopsy liver. These conditions of low antioxidant enzyme activities and iron overload are those which support the accumulation of oxygen free-radicals and DNA damage commonly considered to be carcinogenic mechanisms.
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PMID:Antioxidant systems in tumour cells: the levels of antioxidant enzymes, ferritin, and total iron in a human hepatoma cell line. 350 92

The surfactant system and the antioxidant enzyme system of the fetal lung have chronologically similar developmental patterns and both can be accelerated by the administration of exogenous glucocorticoids. To test whether the antioxidant enzyme system, like the surfactant system, is regulated, at least in part, by endogenous glucocorticoids, we injected pregnant rats for 3 days prior to delivery with metyrapone, an adrenal 11-beta hydroxylase inhibitor which crosses the placenta and blocks endogenous glucocorticoid synthesis, or saline. Metyrapone offspring had significantly decreased lung tissue disaturated phosphatidylcholine/total phospholipids (p less than 0.05) compared to controls at days 21 and 22 of gestation. Activities of the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase were similarly significantly reduced (p less than 0.01) in the lungs of metyrapone offspring at both gestational days studied. One day premature metyrapone pups demonstrated poorer survival than control pups from 25 min after delivery (44% survival versus 83%, p less than 0.05) to 90 min (6% survival versus 78%, p less than 0.01). These findings of delayed maturation of the surfactant and antioxidant enzyme systems following adrenal glucocorticoid blockade suggest that both systems are regulated, at least in part, by an endogenous glucocorticoid mechanism.
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PMID:Metyrapone delays surfactant and antioxidant enzyme maturation in developing rat lung. 375 36

Studies on rats treated for 15 months with ethanol (10%, w/v, solution in drinking water) revealed that the stimulation of hepatic cytochrome P-450 monooxygenases activity was accompanied by enhanced microsomal malondialdehyde formation, a lipid peroxidation index and a decreased level of the antioxidant, alpha-tocopherol. The other components of the prooxidant/antioxidant system, diene conjugates and catalase, glutathione peroxidase and superoxide dismutase activities were unaffected. Oxidative stress in blood was shown by a significant decrease in the alpha-tocopherol level whereas lipid peroxidation and antioxidant enzyme activity remained unchanged. The prooxidative effect of ethanol was catalytically promoted by an iron overload (Fe-saccharate, 100 mg Fe3+/kg body wt. intraperitoneally, 2, 5 and 7 day before test) to simulate the effect of alcoholic hemochromatosis. Thus, the level of malondialdehyde and alpha-tocopherol in the serum may be recommended as biological markers of ethanol-provoked oxidative stress, which is especially useful in the evaluation of the combined effect of ethanol and other chemicals that affect the redistribution of active iron complexes.
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PMID:Biological markers of oxidative stress induced by ethanol and iron overload in rat. 771 62

The effect of dietary iron levels on iron status, blood lipids and endogenous antioxidants was investigated in male and female rats. Diets low in iron (15 mg/kg Fe; LFe) or high in iron (400 mg/kg Fe; HFe) were given to groups of male (n = 6) and female (n = 6) weanling rats for six weeks. In a second experiment the same dietary iron levels were fed to groups (n = 12) of males and females for seven months, during which colon tumours were induced. Indices of iron status, blood lipid levels and antioxidant enzyme activities were measured in both experiments. In the first experiment, indices of iron status were significantly higher in HFe rats and in females compared with males. Cholesterol and triglycerides were significantly higher in HFe rats and cholesterol was significantly higher in males. Plasma albumin and bilirubin levels and plasma caeruloplasmin activity were significantly higher in female rats. The second experiment confirmed the higher indices of iron status in HFe rats and in female rats, and also showed that plasma cholesterol levels were significantly higher in HFe rats. There were no consistent, significant differences over both experiments in activities of the antioxidant enzymes measured. Results show that higher dietary iron levels are associated with higher cholesterol levels in male and female rats. However cholesterol was found to be higher in male rats while iron status was higher in female rats. This indicates that factors other than iron status are responsible for the differences in cholesterol in male and female rats.
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PMID:Iron status, blood lipids and endogenous antioxidants in response to dietary iron levels in male and female rats. 788 73

Superoxide dismutase (SOD), which breaks down superoxide to oxygen and hydrogen peroxide, is generally considered an antioxidant enzyme. However, superoxide is a potent reducing agent and as such could affect cellular function by reducing disulfides in important proteins, such as, ionic channels and pumps. In support of this concept, we show that superoxide, generated by two different sources, is able to reduce disulfide bonds in an in vitro model. Depending on the source of superoxide this reduction is accelerated by an unsaturated fatty acid or ferric iron and is inhibited by SOD.
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PMID:Superoxide reduction of a disulfide: a model of intracellular redox modulation? 818 13

Alveolar macrophages (AM) from smokers contain a much higher quantity of intracellular iron than AM from nonsmokers. Since some forms of iron will catalyze the formation of hydroxyl radical (.OH) from superoxide and hydrogen peroxide, the ability of AM derived from smokers and nonsmokers to generate .OH was assessed. No detectable .OH was produced by AM from either source, suggesting that iron sequestration by AM may limit the potential for .OH-mediated lung injury. Consistent with this hypothesis, the ability of bronchoalveolar lavage fluid (BAL) from smokers and nonsmokers to act as an .OH catalyst decreased after exposure to AM. We found that, like AM, human monocyte-derived macrophages (MDM) have the ability to acquire large quantities of iron from small low molecular weight iron chelates as well as decrease the ability of BAL to act as a .OH catalyst. When MDM or AM were exposed to the iron chelates or BAL they were then able to generate .OH after phorbol myristate acetate stimulation. However, when acutely iron-loaded or BAL-exposed MDM were placed in culture, their ability to produce .OH decreased with time to the level of non-iron-exposed controls. This process correlated with iron translocation from the plasma membrane to the cytosol as well as a 3-9-fold increase in cellular ferritin. No increase in antioxidant enzyme levels or induction of the heat shock response was observed. Iron sequestration by macrophages may protect nearby cells from exposure to potentially cytotoxic iron-catalyzed oxidants such as .OH.
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PMID:Iron sequestration by macrophages decreases the potential for extracellular hydroxyl radical formation. 838 3

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

The successful prevention of hydrogen peroxide-induced alveolar permeability alterations and cell injury by transferrin-catalase conjugate is described in this study. Permeability alterations and cell injury were induced in cultured alveolar epithelial monolayers by hydrogen peroxide. Transepithelial transport of a permeability marker, [14C] mannitol, and cellular nuclear fluorescence of a membrane integrity indicator, propidium iodide, were used to quantitate epithelial permeability and damage respectively. Hydrogen peroxide (0.1 - 10 mM) induced a dose-dependent increase in both alveolar permeability and cellular damage; however, the oxidant effect on monolayer permeability did not require prior cell damage. Electron spin resonance measurements using the spin trap 5,5-dimethyl-l-pyrroline-N-oxide indicated the formation of hydroxyl radicals in hydrogen peroxide-treated cells. Chelation of the cellular pool of iron by deferoxamine inhibited radical formation and helped protect the cells from oxidative changes. Prior treatment of the cells with catalase (0.1 U-10 U/ml) had minimal protective effects on cell injury and permeability alterations. In contrast, transferrin-catalase conjugate, at the same concentration range, exhibited much improved protective effects on the cells in response to oxidant stress. This enhanced protection was found to correlate well with an increase in cellular uptake of the enzyme conjugate via the transferrin receptor endocytosis pathway. Effective protection by the enzyme conjugate was shown to require both the antioxidant enzyme moiety and the cognate moiety for the cell surface receptor. These findings indicate the potential therapeutic merit of transferrin-catalase conjugate for the treatment of pathological processes in the lung, whenever oxidative stress is involved.
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PMID:Protection against oxidative injury and permeability alteration in cultured alveolar epithelium by transferrin-catalase conjugate. 861 42

Reactive oxygen species have been implicated in neuronal injury associated with various neuropathological disorders. However, little is known regarding the relationship between antioxidant enzyme capacity and resultant toxicity. The antioxidant pathways of primary cerebrocortical cultures were directly examined using a novel technique that measures pentose phosphate pathway (PPP) activity, which is enzymatically coupled to glutathione peroxidase (GPx) detoxification of hydrogen peroxide (H2O2). PPP activity was quantified from data obtained by gas chromatography/mass spectrometry analysis of released labeled lactate following metabolic degradation of [1,6-(13)C2, 6,6-(2)H2] glucose by cerebrocortical cultures. The antioxidant capacity of these cultures was systematically evaluated using H2O2, and the resultant toxicity was quantified by lactate dehydrogenase release. Exposure of primary mixed and purified astrocytic cultures to H2O2 caused stimulation of PPP activity in a concentration-dependent fashion from 0.25 to 22.2% and from 6.9 to 66.7% of glucose metabolized to lactate through the PPP, respectively. In the mixed cultures, chelation of iron before H2O2 exposure was protective and resulted in a correlation between PPP saturation and toxicity. Conversely, addition of iron, inhibition of GPx, or depletion of glutathione decreased H2O2-induced PPP stimulation and increased toxicity. These results implicate the Fenton reaction, reflect the pivotal role of GPx in H2O2 detoxification, and contribute to our understanding of the etiological role of free radicals in neuropathological conditions.
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PMID:Assessment of the role of the glutathione and pentose phosphate pathways in the protection of primary cerebrocortical cultures from oxidative stress. 863 55


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