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)

To investigate the effects of dietary protein and polyunsaturated fat levels on tissue lipid peroxidation and antioxidative enzymes, Long-Evans male weanling rats were fed either an 8% lactalbumin diet containing 2% (L2), 5% (L5), 10% (L10), 15% (L15) or 20% (L20) soybean oil or a 20% lactalbumin diet containing 5% (N5) or 20% (N20) soybean oil for 8 weeks. The tissue thiobarbituric acid-reactive substances (TBARS) concentrations of the L2 group were similar to those of the N5 group except in plasma in which they were higher. The L5 group generally showed tissue TBARS concentrations comparable to the N20 group. Gradually increasing the dietary soybean oil level in the low protein diet further increased the tissue TBARS concentrations. The L20 group had significantly higher TBARS in RBC, liver, heart, kidney and muscle than the N20 group. The low protein-fed groups had lower activities of glutathione peroxidase (EC 1.11.1.9), superoxide dismutase (EC 1.15.1.1) and glucose-6-phosphate dehydrogenase (EC 1.1.1.49) in liver and catalase (EC 1.11.1.6) in RBC than the N5 group. Compared with the N5 group, the N20 group also showed higher TBARS concentrations and lower activities of certain antioxidative enzymes in some tissues. The antioxidative enzyme activities decreased more drastically with the increasing dietary soybean oil level in the low protein-fed groups than in those fed a normal level of protein. Supplementation of 150 mg/kg of all-rac-alpha-tocopheryl acetate to the L15 diet slightly decreased the TBARS in plasma, heart and liver and restored the depressed activities of RBC superoxide dismutase and catalase. The results indicated that insufficiency of dietary protein aggravates the enhanced production of TBARS and the reduced activities of antioxidant enzyme in rats fed a high soybean oil diet.
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PMID:Protein insufficiency aggravates the enhanced lipid peroxidation and reduced activities of antioxidative enzymes in rats fed diets high in polyunsaturated fat. 156 72

Changes in erythrocyte lipid peroxidation (measured as the concentration of malonyl dialdehyde), glutathione metabolism, antioxidant enzyme activities (glutathione peroxidase, catalase, and superoxide dismutase), the oxidized products of haemoglobin (Hb), and hydrogen peroxide (H2O2)-induced haemolysis were studied in six children with chronic renal failure treated with serial acetate and bicarbonate haemodialysis (HD). Ten age- and sex-matched children acted as controls. Malonyl dialdehyde levels were significantly higher and antioxidant enzyme activities lower in uraemic red blood cells (RBCs) compared with controls (P less than 0.05). Incubation of RBCs for 1 h with acetylphenylhydrazine induced a decrease in the concentration of reduced glutathione (P less than 0.001) and an increase in the level of oxidized products of Hb (P less than 0.001), but only in the uraemic patients. The H2O2 haemolysis test revealed a mild (n = 3) to increased (n = 3) haemolysis in the uraemic RBCs. Oxidative haemolysis is probably a multifactorial process in uraemic patients, and may be an important risk factor in HD therapy.
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PMID:Erythrocyte defense mechanisms against free oxygen radicals in haemodialysed uraemic children. 203 30

Asbestos resembles the phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA), in its ability to elicit release of superoxide (O2-.) from rodent alveolar macrophages (AM) in vitro. In addition, superoxide dismutase (SOD), the antioxidant enzyme scavenging O2-, is increased in cultures of tracheobronchial epithelial cells and lung fibroblasts after exposure to either crocidolite or chrysotile asbestos. Our objectives here were to determine: (1) the chemical and physical properties of asbestos important in the generation of O2- from rat AM; and (2) the effects of O2- in comparison with asbestos on biosyntheses of collagen and non-collagen protein in rat lung fibroblasts in vitro. We were also interested in whether increased production of SOD occurred in the lungs of rats after inhalation of crocidolite asbestos. To determine whether O2- was elicited in response to a variety of asbestiform fibres, AM lavaged from Fischer 344 rat lungs were exposed in vitro to equivalent non-toxic amounts of crocidolite asbestos, erionite, Code 100 fibreglass, sepiolite, and their non-fibrous analogues, riebeckite, mordenite and glass particles. In addition, sized preparations of long (greater than 10 microns) and short (less than 2 microns) asbestos were introduced at identical concentrations to determine whether length of fibres is critical in O2- release. The amount of O2- released from AM in response to dusts was then determined by measuring SOD-inhibitable reduction of cytochrome C. All asbestiform fibres caused a significant (p less than 0.05) increase in generation of O2- from epithelial cells, whereas non-fibrous particles were less active at comparable concentrations. Experiments with long (greater than 10 microns) versus short (less than 2 microns) chrysotile showed that long fibres caused a more striking, dosage-dependent release of O2-. To determine whether O2- plays a role in the causation of fibrotic lung disease, rat lung fibroblasts were exposed to a biochemical generation system (xanthine-xanthine oxidase) for O2- before quantitation of cell-associated collagen and non-collagen protein at 24, 48 and 72 h thereafter. At the latter time periods, significant increases in total collagen per ng DNA were observed. In comparison with controls, the generation system for O2- also caused an initial decrease in synthesis of non-collagen protein followed by increases in synthesis of non-collagen protein at 48 and 72 h.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Mechanisms of fibre-induced superoxide release from alveolar macrophages and induction of superoxide dismutase in the lungs of rats inhaling crocidolite. 254 20

Evidence has been obtained that implicates the generation of reactive oxygen species as an early and critical event in the promotion of neoplastic transformation in mouse JB6 cells. The time courses for specific inhibition by CuZn-superoxide dismutase (CuZn-SOD) of the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced promotion of neoplastic transformation in JB6 cells and for changes in antioxidant enzyme activities associated with TPA-exposure were examined. The antipromoting effect of CuZn-SOD was found to be critically dependent on the time of addition of CuZn-SOD relative to the start of a 14-day exposure of cells to TPA. Treatment of JB6 P+ Clone 22 and Clone 41 cells with CuZn-SOD for 18 h before, simultaneously with or up to 1 h after exposure to TPA, all inhibited promotion of transformation maximally. Delay of addition of CuZn-SOD by 2 h or more after the start of TPA treatment resulted in a marked decrease in the promotion inhibitory effect. CuZn-SOD added 24 or 48 h after TPA had no effect on promotion of transformation. Exposure of JB6 cells to 0.2- (superoxide anion radical) generated exogenously by the aerobic xanthine oxidase reaction resulted in promotion of neoplastic transformation that was prevented by concurrent addition of CuZn-SOD. Taken together these studies provide evidence that increased superoxide anion generation within the first 2 h following TPA exposure is an essential event in promotion of transformation in JB6 cells. Upon TPA exposure, JB6 Clone 41 cells exhibited time-specific activity changes in the cellular SOD, glutathione peroxidase (GSH-Px), and catalase. SOD and GSH-Px activities were reduced to 54% and 26% respectively of basal levels within 2 h of TPA treatment. GSH-Px activity recovered to basal levels within 4 h and CuZn-SOD within 48 h. Catalase activity was maximally reduced to 50% of basal within 1 h after TPA treatment and rebounded to greater than basal levels within 4 h. It is postulated that a c-kinase-dependent event induces rapid elevation of superoxide anion following TPA exposure and that this leads to reduced activity of antioxidant enzymes. Since antipromotion by exogenous CuZn-SOD is effective only during the first 2 h following TPA exposure, this suggests that the promotion-relevant 0.2- elevation is transient.
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PMID:Early superoxide dismutase-sensitive event promotes neoplastic transformation in mouse epidermal JB6 cells. 282 3

We have used the HL-60 and PLB-985 myeloid leukemia cell lines to examine the regulation of expression of the important intracellular antioxidant enzyme, glutathione peroxidase (GSH-Px), during phagocytic cell differentiation in vitro. Induction of differentiation along the monocytic pathway by phorbol ester results in an approximately twofold rise in enzyme activity and a parallel increase in the rate of 75Se incorporation into immunoprecipitable GSH-Px protein. Induction along the granulocytic pathway by dimethyl formamide (DMF) results in similar changes in steady-state enzyme levels and rates of GSH-Px protein synthesis. Steady-state levels of GSH-Px gene transcripts also increase more than twofold, approximately in parallel with the enzyme levels. Nuclear run-on transcription assays of GSH-Px mRNA synthesis show ratios of induced to uninduced transcript levels of 2.24 and 1.59 with phorbol myristate acetate (PMA) induction and DMF, respectively, in HL-60 cells, and ratios of 1.34 and 3.46 with PMA and DMF, respectively, in PLB-985 cells. Half lives of GSH-Px mRNA are unchanged or slightly shorter after differentiation of HL-60 cells, and slightly longer after induction of PLB-985. Overall, the present studies show that GSH-Px activity rises during in vitro-induced monocytic or granulocytic differentiation of myeloid cell lines and that the increased expression of the cellular GSH-Px gene occurs through complex mechanisms that include transcriptional up-regulation. This pattern contrasts with the nearly complete cotranslational regulation of GSH-Px expression by exogenous selenium.
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PMID:Regulation of the human cellular glutathione peroxidase gene during in vitro myeloid and monocytic differentiation. 794 46

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

The authors studied the effect of alpha-tocopherol acetate and nicotinamide on lipid peroxidation and antioxidant enzyme defense (AED) in red cell membranes of 61 patients with new-onset insulin-dependent diabetes mellitus. Lipid peroxidation products were found in excessive quantities, whereas enzymes of the cell antioxidant defense were on the decrease. Combination of tocopherol with nicotinamide as adjuvants to conventional insulin therapy promoted normalization of lipid peroxidation and AED, improving beta-cell function. It is believed justified to introduce antioxidant treatment early in the disease onset to prevent toxic damage to beta-cells and vascular endothelium induced by lipid peroxidation products.
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PMID:[Treatment with thymogen and myelopid of patients with bronchial asthma]. 869 81

Reactive oxygen species of mitochondrial origin have been implicated in regulating the expression of several tumor necrosis factor (TNF)-induced genes. Manganese superoxide dismutase (Mn-SOD) is one of many genes, but only antioxidant enzyme, induced in response to tumor necrosis factor. Mn-SOD is a nuclear-encoded mitochondrial matrix protein and serves a protective function by detoxifying superoxide. To address the role of superoxide in regulating gene expression in response to TNF, we have constitutively overexpressed Mn-SOD in a human fibrosarcoma cell line and asked what effect this has on the expression of a number of TNF-responsive genes using reverse transcription-polymerase chain reaction. Of the TNF-induced transcripts analyzed, only interleukin-1alpha (IL-1alpha) was modulated in response to Mn-SOD overexpression. In all cases of Mn-SOD overexpression, IL-1alpha protein and mRNA levels were lowered constitutively and in response to TNF when compared to the parental and mock-transfected cell lines. The induction of IL-1alpha by TNF can also be decreased by growth in 3% oxygen as compared to growth in 21% O2; in addition, growth in low oxygen lowers the basal level of IL-1alpha protein. The effect of Mn-SOD overexpression on IL-1alpha expression can be overcome by treatment with the protein kinase C activator, phorbol 12-myristate 13-acetate. Mn-SOD overexpression and low oxygen alter IL-1alpha mRNA levels by decreasing the stability of the IL-1alpha mRNA. These findings indicate that both Mn-SOD and O2 may regulate the levels of a cellular oxidant involved in both basal and TNF-induced IL-1alpha expression, presumably superoxide.
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PMID:Manganese superoxide dismutase modulates interleukin-1alpha levels in HT-1080 fibrosarcoma cells. 870 51

1. During all aerobic metabolism, free radicals generated by the partial reduction of oxygen are potentially injurious to cells. Highly efficient antioxidant defence systems exist to inhibit oxidative damage to cellular lipids and proteins. Specific enzymes have a crucial role in these antioxidant defences, and their activity may be induced by regulatory mechanisms that respond to oxygen metabolite concentration. 2. To assess whether smoking induces an additional adaptive response, we compared antioxidant defence systems in erythrocytes from smokers and non-smokers and assessed whether a high intake of vitamin E (280 mg/day), a major lipophilic free-radical-scavenging antioxidant, affects the activity of antioxidant enzymes. 3. A total of 100 men, 50 smokers and 50 non-smokers, were allocated to four treatment groups in a 2 x 2 factorial design (smokers versus non-smokers and placebo versus vitamin E). For 10 weeks each subject took one capsule per day of either 280 mg dl-alpha-tocopherol acetate or a visually identical placebo (hydrogenated coconut oil with negligible vitamin E content). 4. Despite increased erythrocyte cytosolic antioxidant enzyme activities in smokers compared with non-smokers, erythrocytes from smokers were more susceptible to hydrogen peroxide-induced lipid peroxidation in vitro. 5. Vitamin E supplementation further increased erythrocyte catalase (EC 1.11.1.6) activity in both smokers and non-smokers (P < 0.001) and erythrocyte glutathione peroxidase (EC 1.11.1.9) and glutathione reductase (EC 1.6.4.2) activities in non-smokers (P < 0.001). After supplementation with vitamin E there was a concomitant fall in erythrocyte superoxide dismutase (EC 1.15.1.1) activity (P < 0.001) and total glutathione concentration (P < 0.01). Furthermore, in both smokers and non-smokers there was a significant decrease in the susceptibility of erythrocytes to peroxidation (P < 0.001). 6. Various endogenous and exogenous factors exert control over cellular protection against reactive oxygen species, and our data suggest that one such factor is the supply of vitamin E.
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PMID:Effects of vitamin E supplementation on erythrocyte antioxidant defence mechanisms of smoking and non-smoking men. 877 68

An oxidant-antioxidant imbalance in neonatal alveolar macrophages (AMs) may contribute to the increased susceptibility to lung injury described in the neonatal period. We therefore evaluated oxygen radical production by rat AMs at various postnatal ages, and measured in parallel cellular antioxidant enzyme activities. AMs were obtained by bronchoalveolar lavage from rats aged < 24 h, 21 days and 5 weeks, and results were compared to those obtained with adult rat AMs. Intracellular production of oxygen radical species, estimated fluorometrically using 2',5'-dichlorofluorescein diacetate as the substrate, was significantly reduced in neonates as compared with adults, both in the presence and in the absence of cell stimulation with phorbol myristate acetate (PMA) or opsonized zymosan. A similar pattern was observed for the extracellular release of oxygen radical species, evaluated by lucigenin-enhanced chemiluminescence (CL) or peroxidase-catalysed CL oxidation of luminol: peak CL values measured after cell stimulation with PMA or opsonized zymosan remained significantly lower for AMs from newborn rats than for AMs from adults. By contrast, high values for antioxidant enzyme activities (superoxide dismutase and glutathione peroxidase) in AMs were demonstrated in newborns as compared to adults. We conclude that high antioxidant activity in rat AMs after birth may be at least partly responsible for the low production of oxygen metabolites observed during the same period.
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PMID:Oxidant-antioxidant balance in alveolar macrophages from newborn rats. 898 Sep 63


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