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)

Antioxidant defense system prevents the organism from the detrimental effects of free radicals via scavenging or inhibiting their formation. Changes in the antioxidant defense mechanisms and alterations of several essential trace elements in both plasma and various tissues of ob/ob mice have been reported previously. Recent finding of the restoration of the defective antioxidant enzyme activity after leptin treatment in ob/ob mice suggests a putative role of leptin in modulation of antioxidant enzyme activity. Therefore, the aim of this study was to investigate whether antioxidant enzymes and trace elements could also be altered in patients with leptin gene mutation. Seven patients (five men and two women, two of them are homozygous and 5 are heterozygous) with leptin gene mutation and 31 healthy, sex- and age-matched and non-related to the patients (24 male and 9 female), control volunteers were enrolled in the study. Plasma and erythrocyte glutathione peroxidase (GSH-Px) and erythrocyte copper-zinc superoxide dismutase (CuZn-SOD) activities were measured spectrophotometrically. Plasma selenium (Se), manganese (Mn), zinc (Zn), copper (Cu), and iron (Fe) levels were measured by atomic absorption spectrophotometry. Mean Cu and Fe levels in patients were not significantly different than those in controls whereas mean Se, Zn and Mn levels were significantly lower in patients than those of controls (P=0.007, P=0.001, and P=0.001, respectively). Erythrocyte GSH-Px (39%), plasma GSH-Px (24%) and erythrocyte CuZn-SOD activities (32%) were significantly lower than those of the control group (P=0.001, P=0.002, P=0.001, respectively). In conclusion, our results demonstrate that the activity of antioxidant enzymes and plasma levels of Se, Zn and Mn levels were decreased in both homozygous and heterozygous subjects with leptin gene mutation. We suggest that both leptin and trace elements might be involved in the modulation of antioxidant defense system.
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PMID:Defective antioxidant defense system in patients with a human leptin gene mutation. 1096 32

Administration of supplemental oxygen, despite being an important clinical therapy, can cause significant lung damage. Because they have underdeveloped lungs, prematurely born human infants frequently require supportive therapies that employ elevated oxygen concentrations, which put them at risk for developing pulmonary oxygen toxicity. This risk is made even greater by the immaturity of their cellular antioxidant defenses. Although the exact mechanisms of oxygen toxicity are still not fully defined, cellular damage is probably mediated by increased production of chemically reactive oxygen species (ROS) in the mitochondria. Cellular protection against ROS is provided by a variety of antioxidant molecules and enzymes, including the glutathione (GSH)-dependent antioxidant system. The GSH-dependent antioxidant enzyme system provides vital cellular protection against ROS, particularly hydrogen peroxide and certain organic hydroperoxides, under pathological and toxicological conditions, by using selenium-dependent and -independent peroxidases to reduce hydrogen peroxide or lipid peroxides to water or the respective alcohols, with the concurrent oxidation of GSH to glutathione disulfide (GSSG). In the mitochondria, limitations of GSH synthesis and transmembrane transport suggest that optimal functioning of the mitochondrial GSH system, and maintenance of adequate thiol-disulfide redox tone is essential to protect against the injurious effects of ROS. Manipulation of endogenous GSH concentrations can alter cellular responses to oxidant injury. Beneficial effects are evident when intracellular GSH concentrations are increased. In conditions that increase mitochondrial production of ROS, such as exposure to high concentrations of oxygen, therapies based on enhancing mitochondrial GSH concentrations could be highly beneficial.
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PMID:Mitochondrial glutathione and oxidative stress: implications for pulmonary oxygen toxicity in premature infants. 1100 27

Thioredoxin, thioredoxin reductase and NADPH, the thioredoxin system, is ubiquitous from Archea to man. Thioredoxins, with a dithiol/disulfide active site (CGPC) are the major cellular protein disulfide reductases; they therefore also serve as electron donors for enzymes such as ribonucleotide reductases, thioredoxin peroxidases (peroxiredoxins) and methionine sulfoxide reductases. Glutaredoxins catalyze glutathione-disulfide oxidoreductions overlapping the functions of thioredoxins and using electrons from NADPH via glutathione reductase. Thioredoxin isoforms are present in most organisms and mitochondria have a separate thioredoxin system. Plants have chloroplast thioredoxins, which via ferredoxin-thioredoxin reductase regulates photosynthetic enzymes by light. Thioredoxins are critical for redox regulation of protein function and signaling via thiol redox control. A growing number of transcription factors including NF-kappaB or the Ref-1-dependent AP1 require thioredoxin reduction for DNA binding. The cytosolic mammalian thioredoxin, lack of which is embryonically lethal, has numerous functions in defense against oxidative stress, control of growth and apoptosis, but is also secreted and has co-cytokine and chemokine activities. Thioredoxin reductase is a specific dimeric 70-kDa flavoprotein in bacteria, fungi and plants with a redox active site disulfide/dithiol. In contrast, thioredoxin reductases of higher eukaryotes are larger (112-130 kDa), selenium-dependent dimeric flavoproteins with a broad substrate specificity that also reduce nondisulfide substrates such as hydroperoxides, vitamin C or selenite. All mammalian thioredoxin reductase isozymes are homologous to glutathione reductase and contain a conserved C-terminal elongation with a cysteine-selenocysteine sequence forming a redox-active selenenylsulfide/selenolthiol active site and are inhibited by goldthioglucose (aurothioglucose) and other clinically used drugs.
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PMID:Physiological functions of thioredoxin and thioredoxin reductase. 1101 61

Thioredoxin reductase is a selenoenzyme responsible for maintaining thioredoxin in the reduced form. Because thioredoxin is involved in many cellular processes, thioredoxin reductase is likely to be an important regulatory protein for both normal and transformed cells. Monomethylated selenium compounds inhibit carcinogenesis. In the present study, we investigated whether methylated forms of selenium would alter thioredoxin reductase activity in rats. The liver enzyme was used as a model system. Se-methylselenocysteine and methylseleninic acid consumed by rats at 2 microg Se/g diet for 3, 6, 10 or 22 wk did not affect activity compared with a basal diet containing 0.1 microg Se/g. The direct addition of 50 micromol dimethyl diselenide or dimethyl selenenylsulfide per L to liver extracts significantly inhibited thioredoxin reductase activity by approximately 60%. The magnitude of inhibition was dependent on the amount of thioredoxin in the assay and was reversible by dialysis, suggesting that a competitive type of inhibition occurs in vitro. Although thioredoxin reductase can be inhibited by high levels of selenium in a cell-free system, it should be noted that such a condition is unlikely to be attainable in vivo. Caution needs to be exercised in interpreting the in vitro results.
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PMID:Thioredoxin reductase activity in rat liver is not affected by supranutritional levels of monomethylated selenium in vivo and is inhibited only by high levels of selenium in vitro. 1116 May 50

Thioredoxin reductase (TR) is a flavoenzyme, containing one selenocysteine (Sec) residue at the penultimate carboxyl-terminus, that catalyzes the NADPH-dependent reduction of oxidized thioredoxin. Sec is encoded by the UGA stop codon in the open reading frame of the mRNA, and the conserved stem-loop structure in 3'-untranslated regions functions as the determinant of Sec incorporation instead of termination of translation. The efficiency of Sec incorporation in Sec-containing enzymes in physiological or selenium (Se)-deficient condition remains unclear. To clarify this, we have developed monoclonal antibodies to human TR, and established a sandwich enzyme-linked immunosorbent assay to determine TR protein content. We observed that the specific activity of cytosolic TR in NCI-H441 cells increased with increasing concentrations of Se in a serum-free medium. The specific activity of TR purified from each cytosol was essentially equal to the calculated specific activity of each cytosolic TR. The Se content of TR increased with increasing concentration of Se in the medium, from 0.32 mol/mol of TR subunit (no SE) to 0.98 mol/mol of TR subunit (500 nM Se), and was directly correlated with the specific activity of TR. When calculated from the cytosolic TR specific activity of human peripheral mononuclear cell, the theoretical efficiency of Sec incorporation in physiological conditions is assumed to be 87%.
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PMID:Efficiency of selenocysteine incorporation in human thioredoxin reductase. 1121 69

We have studied the relationship between antioxidant and anticancer properties of selenium (Se) in multistage hepatocarcinogenesis induced by N-nitrosodiethylamine (DEN). In this study we have observed an increased level of lipid peroxide (LPO) products and decreased antioxidant enzyme activities (superoxide dismutase and catalase) in hepatoma and surrounding liver tissues of cancer-bearing animals. Selenium (Se) was supplemented either before initiation or during initiation and selection/promotion phases of hepatocarcinogenesis and was found to be effective in altering hepatic lipid peroxidation and antioxidant enzyme activities to a statistically significant level measured either in the hepatoma or in the surrounding liver tissues. These alterations inclined towards normal in a time-dependent manner on selenium supplementation. Furthermore, increased levels of lipid peroxidation and decreased levels of antioxidants (superoxide dismutase and catalase) were also observed in distant organs of cancer-bearing rats other than the tumour-bearing site. These alterations are brought back to normal levels upon Se treatment. Our results confirm the fact that Se is particularly protective in limiting the action of DEN by its antioxidant property.
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PMID:Effect of selenium on N-nitrosodiethylamine-induced multistage hepatocarcinogenesis with reference to lipid peroxidation and enzymic antioxidants. 1122 68

Erythrocyte, plasma, and serum antioxidant activities were studied in patients with newly diagnosed and untreated toxic multinodular hyperthyroid goiter and compared to healthy control subjects. Erythrocyte antioxidant enzyme activities, glutathione, malondialdehyde, and ceruloplasmin levels were significantly increased, whereas serum vitamin E, plasma vitamin C, and selenium levels were decreased in hyperthyroid patients compared to control subjects. The findings show that untreated toxic multinodular goiter causes profound alterations in components of the antioxidant system in erythrocytes indicative of increased oxidative stress. Taken together, these data suggest that hyperthyroid patients may benefit from dietary supplements of antioxidants.
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PMID:Erythrocyte, plasma, and serum antioxidant activities in untreated toxic multinodular goiter patients. 1129 64

The generation of reactive oxygen species (free radicals) is an important factor in the development and maintenance of rheumatoid arthritis in humans and animal models. One source of free radicals is nitric oxide produced within the synoviocytes and chondrocytes and giving rise to the highly toxic radical peroxynitrite. Several cytokines, including tumour necrosis factor-alpha (TNFalpha) are involved in the formation of free radicals, partly by increasing the activity of nitric oxide synthase. Indeed, nitric oxide may mediate some of the deleterious effects of cytokines on bone resorption. Aspirin, tetracyclines, steroids and methotrexate can suppress nitric oxide synthase. Dietary antioxidants include ascorbate and the tocopherols and beneficial effects of high doses have been reported especially in osteoarthritis. There is also evidence for beneficial effects of beta-carotene and selenium, the latter being a component of the antioxidant enzyme glutathione peroxidase. The polyunsaturated fatty acids (PUFA) include the n-3 compounds, some of which are precursors of eicosanoid synthesis, and the n-6 group which can increase formation of the pro-inflammatory cytokines TNFalpha and interleukin-6, and of reactive oxygen species. Some prostaglandins, however, suppress cytokine formation, so that n-3 PUFA often oppose the inflammatory effects of some n-6-PUFA. gamma-linolenic acid (GLA) is a precursor of prostaglandin E1, a fact which may account for its reported ability to ameliorate arthritic symptoms. Fish oil supplements, rich in n-3 PUFA such as eicosapentaenoic acid have been claimed as beneficial in rheumatoid arthritis, possibly by suppression of the immune system and its cytokine repertoire. Some other oils of marine origin (e.g. from the green-lipped mussel) and a range of vegetable oils (e.g. olive oil and evening primrose oil) have indirect anti-inflammatory actions, probably mediated via prostaglandin E1. Overall, there is a growing scientific rationale for the use of dietary supplements as adjuncts in the treatment of inflammatory disorders such as rheumatoid arthritis and osteoarthritis.
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PMID:Antioxidants and fatty acids in the amelioration of rheumatoid arthritis and related disorders. 1129 72

The expression of the HIV-1 Tat protein in HeLa cells resulted in a 2.5-fold decrease in the activity of the antioxidant enzyme glutathione peroxidase (GPX). This decrease seemed not to be due to a disturbance in selenium (Se) uptake. Indeed, the intracellular level of Se was similar in parental and tat-transfected cells. A Se enrichment of the medium did not lead to an identical GPX activity in both cell lines, suggesting a disturbance in Se utilization. Total intracellular 75Se selenoproteins were analyzed. Several quantitative differences were observed between parental and tat-transfected cells. Mainly, cytoplasmic glutathione peroxidase and a 15-kDa selenoprotein were decreased in HeLa-tat cells, while phospholipid hydroperoxide glutathione peroxidase and low-molecular-mass selenocompounds were increased. Thioredoxin reductase activity and total levels of 75Se-labeled proteins were not different between the two cell types. The effect of Tat on GPX mRNA levels was also analyzed. Northern blots revealed a threefold decrease in the GPX/glyceraldehyde phosphate dehydrogenase mRNA ratio in HeLa-tat versus wild type cells. By deregulating the intracellular oxidant/antioxidant balance, the Tat protein amplified UV sensitivity. The LD50 for ultraviolet radiation A was 90 J/cm2 for HeLa cells and only 65 J/cm2 for HeLa-tat cells. The oxidative stress occurring in the Tat-expressing cells and demonstrated by the diminished ratio of reduced glutathione/oxidized glutathione was not correlated with the intracellular metal content. Cellular iron and copper levels were significantly decreased in HeLa-tat cells. All these disturbances, as well as the previously described decrease in Mn superoxide dismutase activity, are part of the viral strategy to modify the redox potential of cells and may have important consequences for patients.
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PMID:Human immunodeficiency virus type 1 Tat protein impairs selenoglutathione peroxidase expression and activity by a mechanism independent of cellular selenium uptake: consequences on cellular resistance to UV-A radiation. 1136 44

Polychlorinated biphenyls (PCBs) induce drug metabolism that may lead to the bioactivation of PCBs themselves or alternatively may lead to oxidative events within the cell. The goal of the present study was to determine the influence of congeneric PCBs, selected as substrates for or inducers of drug metabolism, upon hepatic glutathione, glutathione-related enzymes, and selenium status. Male and female Sprague-Dawley rats received two i.p. injections per week of PCB 3 (4-chlorobiphenyl), PCB 28 (2,4,4'-trichlorobiphenyl), PCB 38 (3,4,5-trichlorobiphenyl), PCB 77 (3,3',4,4'-tetrachlorobiphenyl), PCB 153 (2,2',4,4',5,5'-hexachlorobiphenyl), or both PCBs 77 and 153 (100 micromol/kg/injection) and were killed at the end of 1, 2, or 3 weeks. Whole liver homogenates, hepatic cytosol, and microsomes were prepared. Both glutathione reductase and glutathione transferase activities were increased significantly in both male and female rats receiving PCB 77, an aryl hydrocarbon receptor agonist, as well as in those receiving both PCBs 77 and 153. No significant trend was observed in the levels of hepatic total glutathione. PCB 77 treatment decreased hepatic selenium-dependent glutathione peroxidase (SeGPX) activity in both male and female rats significantly. This decrease in activity following PCB 77 treatment was accompanied by a decrease in the cytosolic selenium-dependent glutathione peroxidase gene (GSPx1) transcript, as well as a decrease in hepatic total selenium levels. These data support the concept that exposure to the coplanar PCB 77 suppresses, via gene regulatory mechanisms, the cellular antioxidant enzyme SeGPX and that this decrease involves selenium. Lower halogenated PCBs that may be bioactivated to reactive oxygen species (ROS)-producing metabolites, and higher halogenated PCBs that are not Ah receptor agonists, were inactive.
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PMID:Effects of selected polychlorinated biphenyl (PCB) congeners on hepatic glutathione, glutathione-related enzymes, and selenium status: implications for oxidative stress. 1143


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