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 study of free radical biology has engendered a great deal of controversy and apparently conflicting observations, particularly with regard to the use of the antioxidant enzyme superoxide dismutase as a protective or therapeutic agent. Slowly, the reasons behind the confusion are beginning to emerge. The superoxide radical, O2.-, has a number of paradoxical physiological and pathophysiological roles. Several examples of the radical's schizophrenic behavior include its roles in bactericidal action versus inflammation, as a modulator of cell division versus malignant transformation and apoptosis, and as both an initiator and a terminator of lipid peroxidation.
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PMID:Superoxide radical: controversies, contradictions, and paradoxes. 777 Apr 59

Nitric oxide mediates esophageal peristalsis and lower esophageal sphincter (LES) relaxation. Superoxide produced with inflammation inactivates nitric oxide. Superoxide is cleared in biological systems by superoxide dismutase. We tested the hypothesis that superoxide and the superoxide scavenging system modulate LES function. Transverse strips of muscle from the opossum LES relaxed when stimulated by an electrical field. Diethyldithiocarbamite was used to inhibit copper/zinc superoxide dismutase. Xanthine and xanthine oxidase were used to generate superoxide. Xanthine with xanthine oxidase or diethyldithiocarbamite alone had no effect on the LES. However, xanthine/xanthine oxidase and diethyldithiocarbamite reduced LES relaxation 34.1% and increased its resting tone 71.2%. Superoxide dismutase did not affect LES function, but protected the tissue from the effects of diethyldithiocarbamite and xanthine/xanthine oxidase. These studies are consistent with the hypothesis that superoxide acts by inactivating nitric oxide and suggest that these antioxidant enzyme systems may play a role in the maintenance of LES function.
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PMID:Effects of oxygen radicals and radical scavenging on opossum lower esophageal sphincter. 907 44

The carcinogen aniline is negative in the Ames Salmonella mutagenicity assay. Aniline does, however, induce intrachromosomal recombination between repeated sequences in Saccharomyces cerevisiae, resulting in deletion (DEL) of intervening sequences. We have investigated whether the generation of oxidative free radical species by aniline and/ or its metabolites may be responsible for its recombinagenic activity in yeast. The toxicity and recombinagenicity of aniline in yeast were greatly reduced in the presence of the free radical scavenger N-acetyl cysteine. Aniline cytotoxicity was many-fold increased in strains of S.cerevisiae lacking the antioxidant enzyme superoxide dismutase. Aniline also induced oxidation of the intracellular free radical-sensitive reporter compound 2,4-dichlorofluorescin diacetate to its fluorescent derivative 2,4-dichlorofluorescein in vivo in S.cerevisiae. The aniline metabolites 4-aminophenol and 2-aminophenol were significantly more potent inducers of DEL recombination in yeast than aniline. In contrast, the secondary metabolite 4-acetamidophenol (acetaminophen) was non-toxic and non-recombinagenic in yeast. 4-Aminophenol and 2-aminophenol were also significantly more toxic than aniline in a superoxide dismutase deficient yeast strain. 4-aminophenol was a significantly more potent oxidizer of 2,4-dichlorofluorescin diacetate than aniline. The Escherichia coli soxS promoter, which is induced in the presence of redox cycling agents like paraquat, was induced weakly by aniline at toxic doses. The soxS promoter was strongly induced by 4-aminophenol and 2-aminophenol. The results indicate a role for oxidative stress, mediated by generation of superoxide radical, in the toxicity and recombinagenicity of aniline. The increased activity of 4-aminophenol and 2-aminophenol suggests that ring hydroxylation may be an important activating step in this process.
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PMID:Aniline and its metabolites generate free radicals in yeast. 923 64

This study shows that superoxide dismutase is present in the thyroid gland of pigeons as a constitutive enzyme serving as an antioxidant against oxygen toxicity. Exogenous administration of thyrotropin induced thyroidal superoxide dismutase with a simultaneous burst in superoxide anion radical levels during the initial phase of hormone treatment. The superoxide radical generated was completely scavenged by SOD during the late phase of TSH-treatment, presumably as an adaptive measure to check the oxygen burst. TSH failed to augment serum T3 levels, although the thyroxine level in the serum was elevated. The peak level of SOD activity profile in the thyroid gland correlated very well with the peak level of thyroxine concentrations in the serum of pigeon. It is reasonable to postulate that the thyroidal SOD in homeotherms serves a dual role, firstly as a strategic antioxidant enzyme to protect the thyroid gland against the degenerative influence of toxic oxyradicals and secondly to provide H2O2 for thyroid hormone biosynthesis. Our results confirm the previous observations that TSH is mainly thyrotropic in birds and that it has no influence on the peripheral activation of thyroxine to triiodothyronine by stimulating the extra thyroidal 5'-deiodinase activity.
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PMID:Regulation of superoxide anion radical-superoxide dismutase system in the avian thyroid by TSH with reference to thyroid hormonogenesis. 934 97

Much evidence exists in support of the hypothesis that free radicals contribute to the pathogenesis of several neurodegenerative disorders and that mechanisms of free radical generation occur both intracellularly and extracellularly. Previous studies in this laboratory have shown that covalent modification of growth factors and antioxidant enzymes with the naturally occurring polyamine, putrescine, increases their permeability at the blood-nerve and blood-brain barriers (BNB and BBB), but does not significantly inhibit bioactivity. Furthermore, putrescine-modified superoxide dismutase (SOD) was shown to reduce neurodegeneration in a rat model of global cerebral ischemia. The purpose of the present study was to modify the antioxidant enzyme, catalase (CAT), with putrescine (PUT) at carboxylic acid groups whose ionization, and hence reactivity, was controlled with pH and investigate the effects on permeability and enzymatic activity. Modification of CAT with PUT increased its permeability 2-3-fold and preserved 67% of its enzymatic activity compared to native CAT and 137% compared to lyophilized CAT. The results of this study indicate that modification of CAT with putrescine increases its permeability while preserving enzymatic activity. PUT-SOD administered in combination with PUT-CAT may eliminate both the superoxide radical and the H2O2 produced from the dismutation of superoxide, respectively, and thus prevent the formation of hydroxyl radicals. This combination may exhibit increased neuroprotective effects, compared to native enzymes, following systemic administration for the treatment of free radical associated neurodegenerative disorders.
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PMID:Putrescine-modified catalase with preserved enzymatic activity exhibits increased permeability at the blood-nerve and blood-brain barriers. 936 24

It has been suggested that aluminium stimulates vanadium-mediated superoxide radical generation. The oxidative stress of generated superoxide radicals on antioxidant enzyme activity, oxidation of NADH and NADPH, membrane lipid peroxidation and osmotic fragility in human red blood cells (RBC) was investigated. RBC were incubated with varying concentrations of vanadium and aluminium ions at 37 degrees C for 2 h. RBC incubated with vanadium ions showed significantly increased superoxide dismutase and catalase activities, and oxidized NADH and NADPH concentrations compared with control RBC preparations. Erythrocyte lipid peroxidation was assessed by measuring thiobarbituric acid reactivity. RBC incubated with elevated levels of vanadium showed significantly increased membrane lipid peroxidation when compared with control RBC; it increased further on addition of aluminium. A significant positive correlation was observed between the extent of vanadium induced membrane lipid peroxidation and the osmotic fragility of treated RBC. In the presence of vanadium, aluminium stimulates superoxide dismutase and catalase activities. NADH and NADPH oxidation and membrane lipid peroxidation, as well as increasing osmotic fragility of human erythrocytes. The stimulatory effect of aluminium was dependent on concentration. These results may have implications for the mechanism of toxicity of aluminium and vanadium in haemodialysis patients.
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PMID:Oxidative stress of vanadium-mediated oxygen free radical generation stimulated by aluminium on human erythrocytes. 954 97

We found previously that 8-hydroxyguanine (oh8Gua) endonuclease in E. coli is induced in response to oxidative stress in a fashion similar to the oxidative response of the Mn-superoxide dismutase (MnSOD). In this study, attempts were made to identify the genes involved in the co-regulation of E. coli endonuclease and MnSOD (sodA). oh8Gua nuclease is induced by molecular oxygen and a superoxide radical generator (paraquat) but not by H2O2, suggesting that the regulation of this endonuclease is dependent on SoxRS but independent of OxyR. This enzyme was induced by paraquat in all of the soxRS mutant strains used (soxR-, soxS- and soxRc), whereas glucose-6-phosphate dehydrogenase (a member of the soxRS regulon) showed the expected responses; therefore, this possibility was excluded. The presence of metal chelators in the growth medium caused the induction of this enzyme, and this induction was suppressed by the addition of Fe++. Consistent with this finding, this enzyme was expressed under anaerobiosis in all of the mutant strains of fnr in particular, as well as fur, arcA, and combinations thereof. These findings suggest that the oxidative regulation of oh8Gua endonuclease is under control of fnr, fur, and arcA, where fnr plays a predominant role. The multiple involvement of regulatory genes as well as co-regulation with antioxidant enzyme will enhance the efficiency of cellular growth and survival in the aerobic environment.
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PMID:Mechanism of regulation of 8-hydroxyguanine endonuclease by oxidative stress: roles of FNR, ArcA, and Fur. 962 74

Oxygen free radicals have been hypothesized to play an important role in the aging process. To investigate the correlation between the oxidative stress and aging, we have determined the levels of oxidative protein damage and lipid peroxidation in the brain and liver, and activities of antioxidant enzymes in the brain, liver, heart, kidney, and serum from the Fisher 344 rats at ages of 1, 6, 12, 18, and 24 months. The results showed that the level of oxidative protein damage (measured as carbonyl content) in the brain and liver was significantly higher in older animals than in young animals. No statistical difference was observed in the lipid peroxidation of the liver and brain between young and old animals. The activities of antioxidant enzymes in most tissues displayed an age-dependent decline. Superoxide dismutases in the heart, kidney, and serum, glutathione peroxidase activities in the serum and kidney, and catalase activities in the brain, liver, and kidney, significantly decreased during aging. Cytochrome c oxidase, an enzyme involved in electron transport in mitochondria, initially increased, but subsequently decreased in the aged brain, whereas no significant alteration was observed in the liver mitochondrial antioxidant enzymes. The present studies suggest that the accumulation of oxidized proteins during aging is most likely to be linked with an age-related decline of antioxidant enzyme activities, whereas lipid peroxidation is less sensitive to predict the aging process.
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PMID:Alterations of antioxidant enzymes and oxidative damage to macromolecules in different organs of rats during aging. 964 Dec 66

Although researchers in radiation and cancer biology have known about the existence of free radicals and their potential role in pathobiology for several decades, cardiac biologists only began to take notice of these noxious species in the 1970s. Exponential growth of free radical research occurred after the discovery of superoxide dismutase in 1969. This antioxidant enzyme is responsible for the dismutation of superoxide radical--a free radical chain initiator. A fine balance between free radicals and a variety of endogenous antioxidants is believed to exist. Any disturbance in this equilibrium in favour of free radicals causes an increase in oxidative stress and initiates subcellular changes leading to cardiomyopathy and heart failure. Our knowledge about the role of free radicals in the pathogenesis of cardiac dysfunction is fast approaching the point where newer therapies employing antioxidants are in sight.
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PMID:The role of oxidative stress in the genesis of heart disease. 1053 10

Cytochrome c peroxidase oxidises hydrogen peroxide using cytochrome c as the electron donor. This enzyme is found in yeast and bacteria and has been also described in the trematodes Fasciola hepatica and Schistosoma mansoni. Using partially purified cytochrome c peroxidase samples from Fasciola hepatica we evaluated its role as an antioxidant enzyme via the investigation of its ability to protect against oxidative damage to deoxyribose in vitro. A system containing FeIII-EDTA plus ascorbate was used to generate reactive oxygen species superoxide radical, H2O2 as well as the hydroxyl radical. Fasciola hepatica cytochrome c peroxidase effectively protected deoxyribose against oxidative damage in the presence of its substrate cytochrome c. This protection was proportional to the amount of enzyme added and occurred only in the presence of cytochrome c. Due to the low specific activity of the final partially purified sample the effects of ascorbate and calcium chloride on cytochrome c peroxidase were investigated. The activity of the partially purified enzyme was found to increase between 10 and 37% upon reduction with ascorbate. However, incubation of the partially purified enzyme with 1 mM calcium chloride did not have any effect on enzyme activity. Our results showed that Fasciola hepatica CcP can protect deoxyribose from oxidative damage in vitro by blocking the formation of the highly toxic hydroxyl radical (.OH). We suggest that the capacity of CcP to inhibit .OH-formation, by efficiently removing H2O2 from the in vitro oxidative system, may extend the biological role of CcP in response to oxidative stress in Fasciola hepatica.
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PMID:Characterisation of Fasciola hepatica cytochrome c peroxidase as an enzyme with potential antioxidant activity in vitro. 1040 59


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