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)

A thiol-specific antioxidant enzyme (TSA), which provides protection against the inactivation of other enzymes by the thiol/Fe(III)/oxygen system, was previously isolated and cloned. We investigated the mechanism by which TSA protects biomolecules from oxidative damage caused by the thiol-containing oxidation system using the spin trapping method with 5,5-dimethyl-1-pyrroline N-oxide (DMPO). Thiyl radicals from dithiothreitol (.DTT) were produced by horseradish peroxidase/H2O2 under aerobic and anaerobic conditions and by the Fe(III)/oxygen system. The formation of DMPO-.DTT radical adducts were inhibited by TSA regardless of the thiyl radical-generating conditions used. The active mutant C170S also quenched the signals of the radical adduct, whereas the inactive mutant C47S did not exert any effect. It was also found that C170S has a higher rate at the initial stage of the reaction than that of the native enzyme, although C170S failed to remove DMPO-.DTT radical adducts completely. These results indicate that only active TSA can catalyze the removal of thiyl radicals, and cysteine 47 is required for this activity. In addition, thiyl radicals react with oxygen to generate unidentified thiylperoxy species. Fe.EDTA reacts with this species to generate a reactive radical that can abstract hydrogen atom from ethanol to produce a hydroxyethyl radical. This reactive thiyl-oxygen radical is believed to be responsible for causing deleterious effects on biomolecules. Together, our data indicate that TSA protects biomolecules from oxidative damage by catalyzing the removal of thiyl radicals before they generate more reactive radicals. However, presently we cannot rule out the possibility that TSA can also use other thiol-containing species as substrates.
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PMID:On the protective mechanism of the thiol-specific antioxidant enzyme against the oxidative damage of biomacromolecules. 829 8

In the present study, we investigated the effects of high levels of dietary fish oil on the growth of MX-1 human mammary carcinoma and its response to mitomycin C (MC) treatment in athymic mice. We found that high levels of dietary fish oil (20% menhaden oil + 5% corn oil, w/w) compared to a control diet (5% corn oil, w/w) not only lowered the tumor growth rate, but also increased the tumor response to MC treatment. We also found that high levels of dietary fish oil significantly increased the activities of tumor xanthine oxidase and DT-diaphorase, which are proposed to be involved in the bioreductive activation of MC. Since menhaden oil is highly unsaturated, its intake caused a significant increase in the degree of fatty acid unsaturation in tumor membrane phospholipids. This alteration in tumor membrane phospholipids made the tumor more susceptible to oxidative stress, as indicated by the increased levels of both endogenous lipid peroxidation and protein oxidation after feeding the host animals the menhaden oil diet. In addition, the tumor antioxidant enzyme activities, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPOx), and glutathione S-transferase peroxidase (GSTPx), were all significantly enhanced by feeding a diet high in fish oil. MC treatment caused further increases in tumor lipid peroxidation and protein oxidation, as well as in the activities of CAT, SOD, GPOx, and GSTPx, suggesting that MC causes oxidative stress in this tumor model which is exacerbated by feeding a diet high in menhaden oil. Thus, feeding a diet rich in menhaden oil decreased the growth of human mammary carcinoma MX-1, increased its responsiveness to MC, and increased its susceptibility to endogenous and MC-induced oxidative stress, and increased the tumor activities of two enzymes proposed to be involved in the bioactivation of MC, that is, DT-diaphorase and xanthine oxidase. These findings support a role of these two enzymes in the bioactivating of MC and indicate that the type of dietary fat may be important in tumor response to therapy.
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PMID:Dietary menhaden oil enhances mitomycin C antitumor activity toward human mammary carcinoma MX-1. 856 32

E. coli thiol peroxidase (Tpx) linked to the thioredoxin as an in vivo thiol regenerating system acts as an antioxidant enzyme removing peroxides and H2O2. In order to elucidate the mechanism regulating tpx gene expression in E. coli in response to oxygen stress, we made 5' progressive deletions of upstream region from tpx gene, and fused to lacZ gene. LacZ activity was increased 6-fold by oxygen stress and inverted repeat sequence located between -47 and -33 nt was proven to be essential for the oxygen response of tpx promoter. Primer extension experiment and analysis of upstream sequence revealed transcription start point, -10, and -35 regions, which are in good agreements with the consensus sequences recognized by E sigma 70. Northern hybridization showed that expression of tpx gene is regulated at the transcriptional level. DNA binding assays using inverted repeat sequence including -35 region provides preliminary evidence that expression of tpx requires additional transcriptional factor in response to oxygen stress.
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PMID:Identification of promoter in the 5'-flanking region of the E. coli thioredoxin-linked thiol peroxidase gene: evidence for the existence of oxygen-related transcriptional regulatory protein. 863 14

The possible relationship of selenium to immunological function which has been suggested for decades was investigated in studies on selenium metabolism in human T cells. One of the major 75Se-labeled selenoproteins detected was purified to homogeneity and shown to be a homodimer of 55-kDa subunits. Each subunit contained about 1 FAD and at least 0.74 Se. This protein proved to be thioredoxin reductase (TR) on the basis of its catalytic activities, cross-reactivity with anti-rat liver TR antibodies, and sequence identities of several tryptic peptides with the published deduced sequence of human placental TR. Physicochemical characteristics of T-cell TR were similar to those of a selenocysteine (Secys)-containing TR recently isolated from human lung adenocarcinoma cells. The sequence of a 12-residue 75Se-labeled tryptic peptide from T-cell TR was identical with a C-terminal-deduced sequence of human placental TR except that Secys was present in the position corresponding to TGA, previously thought to be the termination codon, and this was followed by Gly-499, the actual C-terminal amino acid. The presence of the unusual conserved Cys-Secys-Gly sequence at the C terminus of TR in addition to the redox active cysteines of the Cys-Val-Asn-Val-Gly-Cys motif in the FAD-binding region may account for the peroxidase activity and the relatively low substrate specificity of mammalian TRs. The finding that T-cell TR is a selenoenzyme that contains Se in a conserved C-terminal region provides another example of the role of selenium in a major antioxidant enzyme system (i.e., thioredoxin-thioredoxin reductase), in addition to the well-known glutathione peroxidase enzyme system.
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PMID:Selenocysteine, identified as the penultimate C-terminal residue in human T-cell thioredoxin reductase, corresponds to TGA in the human placental gene. 865 Feb 34

Glutathione peroxidase is an antioxidant enzyme found in a diverse array of eukaryotic species. We have determined the DNA sequence of a glutathione peroxidase homolog in the pathogenic bacterium Neisseria meningitidis. The sequence displays features of a functional gene, but lacks a selenocysteine-encoding in-frame TGA codon characteristic of most mammalian glutathione peroxidase genes. The derived amino acid sequence encoded by the N. meningitidis homolog predicts a 19.9 kDa protein that displays a high level of amino acid identity with other gluathione peroxidase sequences, particularly within four conserved regions of the enzyme.
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PMID:Identification of a glutathione peroxidase homolog in Neisseria meningitidis. 874 63

It has been found that gonads of sharks contain higher content of alkoxylipids and vitamin K and lower levels of monoglycerides and carotenoids than gonads of teleost fishes. The peroxidase activity is higher in gonads of shark males but the glutathione reductase activity is lower. No significant differences in lipids peroxidation indices in gonads of elasmobranchia and teleosts were found. The total antioxidant activity of lipids in gonads of shark males exceeds 1, while the same indices of teleosts are below 1. Differences in the lipid composition, antioxidant enzyme activities, the content of glutathione, carotenoids, vitamins A, E, K and lipid peroxidation in male and female fish gonads are described. Correlation coefficients for all indices of the lipid peroxidation and antioxidant activity are estimated.
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PMID:[The ratio of processes of lipid peroxidation and antioxidant activity in gonads of Elasmobranchia and teleost fishes of the Black Sea]. 883 Apr 40

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

Plasma levels of 17 beta-estradiol (E2) and malondialdehyde and erythrocyte antioxidant enzyme [superoxide dismutase, catalase, and glutathione-peroxidase (GSH-Px)] activities were evaluated in 20 healthy eumenorrhoic women (EW) on day 7 of the menstrual cycle and in 48 secondary hypothalamic amenorrhea patients (AP) (time 0). The AP were randomly divided into four subgroups of 12 subjects and treated with transdermal E2 for 30 days (subgroup A), oral medroxyprogesterone-acetate for 30 days (subgroup B), and transdermal E2 plus medroxyprogesterone-acetate for 30 days (subgroup C). The fourth subgroup acted as control. E2 and malondialdehyde plasma levels and superoxide dismutase, catalase, and GSH-Px activities were evaluated in subgroups A, B, and C on day 30 of therapy and in the control subgroup. GSH-Px activity was significantly higher in EW than in AP at time 0. A statistically significant increase in E2 plasma levels and GSH-Px activity was observed in subgroups A and C on day 30 of treatment, and there was a significant positive correlation between E2 plasma levels and GSH-Px activity in both subgroups. After a month of treatment, erythrocyte GSH-Px activity in subgroups A and C was not significantly different from that observed in EW. After a month of treatment, no significant variation was found in subgroup B nor in the control group. These results strongly suggest that when plasma E2 is restored to physiological levels in AP, it stimulates erythrocyte GSH-Px activity. Progesterone therapy did not induce significant modifications.
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PMID:Effects of estradiol and medroxyprogesterone-acetate treatment on erythrocyte antioxidant enzyme activities and malondialdehyde plasma levels in amenorrhoic women. 898 54

Highly polyunsaturated fatty acids of the n-3 family are known to be inhibitors of platelet functions, but these fatty acids (FA) may alter the platelet antioxidant status, depending on their concentrations. The present study was aimed to investigate the effect of various FA on glutathione-dependent peroxidase (GPx), the required antioxidant enzyme for degrading FA hydroperoxides. Human platelets were enriched in vitro with either n-3 (18:3, 20.5, or 22.6), n-6 (18:2 or 18:3) FA, 18:1 n-9 or 16:0, and the GPx activity was then measured. It was found that n-3 FA enhanced the GPx activity whereas the others did not affect the enzyme activity. The increased GPx activity was associated with an increased amount of the enzyme measured by Western blotting. The enhanced activity and amount of GPx induced by 22:6n-3, the most potent activator among the n-3 FA, was completely abolished in the presence of cycloheximide at a concentration known to inhibit platelet protein synthesis. Because platelets are devoid of nucleus, which rules out the involvement of transcriptional factors, this suggests that 22:6n-3 might act at a translational level. On the other hand, 22:6n-3 treatment increased the malondialdehyde formation and decreased the vitamin E level in platelets, both events that could be prevented by the antioxidant epicatechin. Because epicatechin also suppressed the enhancement of both the activity and amount of GPx induced by 22:6n-3, we conclude that the increased GPx activity (possibly via protein synthesis) might be associated with an oxidative stress induced by 22:6n-3 and/or 20:4n-6 released from the platelet endogenous pool in the course of the 22:6n-3 enrichment.
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PMID:Effects of fatty acids on human platelet glutathione peroxidase: possible role of oxidative stress. 910 98

A novel antioxidant enzyme designated scavengase p20 was identified in various pathogenic bacteria through database searching for sequences strikingly homologous to a recently discovered Escherichia coli thiol peroxidase p20. The direct biochemical evidence for the existence of scavengase p20 in Haemophilus influenzae, Streptococcus pneumoniae and Helicobacter pylori was provided by protein microsequencing and by in vitro assays for antioxidant activities. Overlapping genes encoding scavengase p20 and superoxide dismutase were recognized in H. pylori and their functional implications are discussed.
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PMID:Scavengase p20: a novel family of bacterial antioxidant enzymes. 914 76


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