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)

Chronic benzaldehyde exposure is known to cause central nervous system (CNS) disturbances. Previous studies have shown that benzaldehyde causes the formation of reactive oxygen species (ROS) in rat synaptosomal fractions. Benzaldehyde has also been implicated in ROS formation in the CNS of rats treated with toluene. We have found that benzaldehyde effectively inactivates the antioxidant enzyme glutathione peroxidase (Ki approximately 15 microM), but has no effect on the other antioxidant enzymes tested: catalase, superoxide dismutase, and glutathione reductase. This effect has been found to be specific to benzaldehyde since other structurally related and unrelated aldehydes tested were found to be devoid of inactivating capacity toward glutathione peroxidase. Since glutathione peroxidase is the main enzyme responsible for removal of hydrogen peroxide and organic hydroperoxides in brain, its inactivation by benzaldehyde may be a main contributor to the observed ROS formation and the observed neurotoxicity caused by either benzaldehyde or toluene exposure.
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PMID:Inactivation of glutathione peroxidase by benzaldehyde. 897 63

Experiments on rats with experimental streptosotocin-induced diabetes have shown intensification of the lipid peroxidation processes and reduction of activity of antioxidant defensive enzymes. The content of G-SH and glutathione peroxidase activity has decreased in comparison with the normal rate by 69% and 28%, respectively. Glutathione reductase activity has risen by 20%. Activity of the antioxidant enzymes (superoxide dismutase, catalase) has reduced and the amount of the final product of lipid peroxidation, MDA has increased. Injection of nicotinamide to diabetic rats (200 mg/1 kg of weight) for 14 days normalized activity of the antioxidant enzyme system and the content of the lipid peroxidation products.
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PMID:[The effect of nicotinamide on the enzymatic activity of the antioxidant defense in experimental diabetes]. 900 53

The effect of endurance training on glutathione (GSH) status and antioxidant enzyme system was investigated in skeletal muscle, heart, and liver of female Sprague-Dawley rats pair fed an isocaloric diet. Ten weeks of treadmill training (25 m/min, 10% grade for 2 h/day, 5 days/wk) increased citrate synthase activity in the deep vastus lateralis (DVL) and soleus muscles by 79 and 39%, respectively (P < 0.01), but not in the heart or liver. In DVL, GSH content was increased 33% (P < 0.05) with training, accompanied by a 64% (P < 0.05) increase in glutamate content but no change in cysteine. Trained rats showed a 62 and 27% higher GSH peroxidase (GPX) and superoxide dismutase (SOD) activity, respectively (P < 0.05), in DVL compared with control rats. In contrast, GSH content and glutathione reductase (GR) activity in soleus declined with training (P < 0.05), whereas activities of GPX and SOD remained unchanged. Training did not alter GSH status in the liver or plasma but significantly decreased the GSH-to glutathione disulfide ratio in the heart. In addition, GR activity in the liver and GSH sulfur-transferase activity in the heart and DVL were significantly lower in the trained vs control rats DVL muscle had threefold higher gamma-glutamyl transpeptidase activity compared with other tissues; however no significant alteration was observed in the activity of gamma-glutamyltranspeptidase or gamma-glutamylcysteine synthetase in the liver, heart, or skeletal muscle. These data indicate that endurance training can cause tissue- and muscle fiber-specific adaptation of antioxidant systems and that GSH homeostasis in extrahepatic tissues may be determined by utilization and uptake of GSH via the gamma-glutamyl cycle.
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PMID:Adaptations of glutathione antioxidant system to endurance training are tissue and muscle fiber specific. 903 30

Thioredoxin reductase, lipoamide dehydrogenase, and glutathione reductase are members of the pyridine nucleotide-disulfide oxidoreductase family of dimeric flavoenzymes. The mechanisms and structures of lipoamide dehydrogenase and glutathione reductase are alike irrespective of the source (subunit M(r) approximately 55,000). Although the mechanism and structure of thioredoxin reductase from Escherichia coli are distinct (M(r) approximately 35,000), this enzyme must be placed in the same family because there are significant amino acid sequence similarities with the other two enzymes, the presence of a redox-active disulfide, and the substrate specificities. Thioredoxin reductase from higher eukaryotes on the other hand has a M(r) of approximately 55,000 [Luthman, M. & Holmgren, A. (1982) Biochemistry 21, 6628-6633; Gasdaska, P. Y., Gasdaska, J. R., Cochran, S. & Powis, G. (1995) FEBS Lett 373, 5-9; Gladyshev, V. N., Jeang, K. T. & Stadtman, T.C. (1996) Proc. Natl. Acad. Sci. USA 93, 6146-6151]. Thus, the evolution of this family is highly unusual. The mechanism of thioredoxin reductase from higher eukaryotes is not known. As reported here, thioredoxin reductase from human placenta reacts with only a single molecule of NADPH, which leads to a stable intermediate similar to that observed in titrations of lipoamide dehydrogenase or glutathione reductase. Titration of thioredoxin reductase from human placenta with dithionite takes place in two spectral phases: formation of a thiolate-flavin charge transfer complex followed by reduction of the flavin, just as with lipoamide dehydrogenase or glutathione reductase. The first phase requires more than one equivalent of dithionite. This suggests that the penultimate selenocysteine [Tamura, T. & Stadtman, T.C. (1996) Proc. Natl. Acad. Sci. USA 93, 1006-1011] is in redox communication with the active site disulfide/dithiol. Nitrosoureas of the carmustine type inhibit only the NADPH reduced form of human thioredoxin reductase. These compounds are widely used as cytostatic agents, so this enzyme should be studied as a target in cancer chemotherapy. In conclusion, three lines of evidence indicate that the mechanism of human thioredoxin reductase is like the mechanisms of lipoamide dehydrogenase and glutathione reductase and differs fundamentally from the mechanism of E. coli thioredoxin reductase.
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PMID:The mechanism of thioredoxin reductase from human placenta is similar to the mechanisms of lipoamide dehydrogenase and glutathione reductase and is distinct from the mechanism of thioredoxin reductase from Escherichia coli. 910 27

Cross-resistance presents an obstacle in cancer chemotherapy. Cadmium is a potential carcinogen whose exposure has been shown in epidemiological and laboratory experiments to cause lung cancer. Cadmium also induces various forms of resistance in human lung carcinoma cells. This resistance may be shared by antineoplastic agents, which should be a concern for chemotherapy of cadmium-induced lung cancer. In the present study, two subpopulations of human lung carcinoma A549 cells with a different magnitude of resistance to cadmium toxicity were shown to have a parallel resistance to the cytotoxic action of Adriamycin (ADR), an important anticancer drug. Several factors were examined to investigate the mechanism(s) for the cross-resistance, including cellular metallothionein and glutathione (GSH) concentrations, glutathione S-transferase activity, mdr1 expression, and antioxidant enzyme activities including superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. Only cellular GSH content was elevated consistently in the cadmium/ADR-resistant cells relative to the cadmium/ADR-sensitive cells. Treatment with buthionine sulfoximine, a specific inhibitor of GSH synthesis sensitized both cell lines to ADR only when the cellular GSH levels were depleted to about 5% of control. This BSO treatment, however, did not affect cell viability. Further study revealed that the cadmium/ADR-resistant cells have a greater capacity in recovery of cellular GSH content following BSO treatment. The results demonstrate that cross-resistance to ADR exists in cadmium-resistant human lung carcinoma A549 cells, and enhanced GSH synthesis capacity, rather than elevated levels of cellular GSH, may be related to this resistance.
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PMID:Decreased sensitivity to adriamycin in cadmium-resistant human lung carcinoma A549 cells. 911 95

The purpose of this study was to measure resting muscle and blood antioxidant status in untrained (n = 8) and jump-trained (n = 8) humans and to evaluate free radical-mediated muscle damage after a strenuous jump test consisting of six bouts of 30-s continuous jumping separated by 2 min of rest. Resting muscle antioxidant activities [superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione reductase (GR), and manganese SOD] were significantly higher in jump-trained compared with untrained subjects. Blood antioxidant enzyme activities and muscle catalase, however, were not different between the two groups. Creatine kinase activities increased significantly (P < 0.0001) after the jump test in untrained individuals, but remained unchanged in the jump trained. Plasma and muscle malonaldehyde (MDA) after the jump test were not significantly different from rest. These data suggest that jump training is associated with elevated activities of SOD and the coupled enzymes GPX and GR in muscle tissue, but other antioxidants remain unchanged. High-intensity jump exercise induces muscle enzyme leakage in untrained humans, but muscle lipid peroxidation, measured as changes in MDA, was not different in the two groups despite the varied muscle antioxidant enzyme levels.
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PMID:Antioxidant status and lipid peroxidation after short-term maximal exercise in trained and untrained humans. 914 28

The effects of the flavonoids quercetin, myricetin and silymarin on DNA damage and cytotoxicity in human cells were investigated. DNA strand breaks and oxidised pyrimidines were determined using alkaline single cell gel electrophoresis (the comet assay). Inhibition of cell growth was also measured. Caco-2 (colon), HepG2 (liver), HeLa (epithelial) cells and normal human lymphocytes showed different, dose-dependent susceptibilities (in terms of strand breakage) to the various flavonoids, quercetin being the most damaging. This agreed well with the ability of the flavonoids to inhibit cell growth. None of the flavonoids induced DNA base oxidation above background levels. All of the flavonoids under investigation caused depletion of reduced glutathione, which, in the case of quercetin, occurred prior to cell death. Neither cytotoxicity nor genotoxicity was associated with the antioxidant enzyme capacity (glutathione, glutathione reductase, glutathione peroxidase and catalase) of the cells.
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PMID:The effect of dietary flavonoids on DNA damage (strand breaks and oxidised pyrimdines) and growth in human cells. 915 Jul 62

Recent evidence has shown that alcohol as well as exercise induces oxidative stress. However, the combination of both on the cardiac antioxidant system is not known. This study investigates the interactive effects of exercise training and chronic ethanol consumption on the antioxidant system of the rat heart. Male Fisher-344 rats were treated as follows: 1) sedentary control (SC); 2) exercise training (ET) for 6.5 weeks; 3) ethanol (2 g/kg, PO) for 6.5 weeks, and 4) ET plus ethanol for 6.5 weeks. Rats were sacrificed and hearts were isolated. Glutathione (GSH), oxidized glutathione (GSSG), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR), and lipid peroxidation (MDA) were determined in heart tissues. SOD and GSH-Px activities were significantly increased 118% and 148% of SC, respectively, due to ET. GSH level increased 118% of SC in ET rats. GSH-Px activity increased 118% of SC whereas SOD activity and CuZn-SOD protein level and GR activity decreased 87%, 71%, and 90% of SC due to chronic ethanol administration. GSH level decreased 87% of SC and lipid peroxidation increased 149% of SC due to ethanol consumption. GSH-Px activity and GSH levels increased 143% and 130% of SC due to combination of ET and ethanol. This study suggests that ET and chronic ethanol ingestion augments the antioxidant enzyme activity and GSH levels in the heart. This combination reduced the extent of ethanol-induced lipid peroxidation. The data suggest that ET may reduce the extent of the damage caused by ethanol consumption on the myocardium.
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PMID:Response of cardiac antioxidant system to alcohol and exercise training in the rat. 916 Aug 8

4-Hydroxynonenal, a product of oxidative degradation of unsaturated lipids, is an endogenous reactive alpha,beta-unsaturated aldehyde with numerous biological activities. 4-Hydroxynonenal rapidly inactivated glutathione reductase in an NADPH-dependent reaction. Inactivation appears to involve the initial formation of an enzyme-inactivator complex, K(D) = 0.5 microM, followed by the inactivation reaction, k = 1.3 x 10(-2) min(-1). alpha,beta-Unsaturated aldehydes such as acrolein, crotonaldehyde, and cinnamaldehyde also inactivated glutathione reductase, although rates varied widely. Inactivation of glutathione reductase by alpha,beta-unsaturated aldehydes was followed by slower NADPH-independent reactions that led to formation of nonfluorescent cross-linked products, accompanied by loss of lysine and histidine residues. Other reactive endogenous aldehydes such as methylglyoxal, 3-deoxyglucosone, and xylosone inactivated glutathione reductase by an NADPH-independent mechanism, with methylglyoxal being the most reactive. However, 2-oxoaldehydes were much less effective than 4-hydroxynonenal. Inactivation of glutathione reductase by these 2-oxoaldehydes was followed by slower reactions that led to the formation of fluorescent cross-linked products over a period of several weeks. These changes were accompanied by loss of arginine residues. Thus, the sequence of events is different for inactivation and modification of glutathione reductase by alpha,beta-unsaturated aldehydes compared with 2-oxoaldehydes with respect to kinetics, NADPH requirements, fluorescence changes, and loss of amino acid residues. The ability of 4-hydroxynonenal at low concentrations to inactivate glutathione reductase, a central antioxidant enzyme, suggests that oxidative degradation of unsaturated lipids may initiate a positive feedback loop that enhances the potential for oxidative damage.
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PMID:Inactivation of glutathione reductase by 4-hydroxynonenal and other endogenous aldehydes. 917 18

Prenatal administration of dexamethasone (Dex) and thyrotropin-releasing hormone (TRH) synergistically enhances lung maturity, but TRH suppresses the antioxidant enzyme activity. Prenatal hormonal therapy improves alveolar surfactant content and lung compliance in rats with congenital diaphragmatic hernia (CDH). In full term neonatal rats with CDH we studied the effects of prenatal Dex or Dex+TRH on antioxidant enzyme activity at birth, on survival, and on lung morphometry after 4 h of ventilation with 100% O2. CDH was induced by administration of 2,4-dichlorophenyl-p-nitro-phenylether (Nitrofen) on gestational day 10. Dex+TRH-treated CDH rats had lower activity of glutathione reductase after birth than did sham-treated CDH pups. Dex-treated and sham-treated pups had similar antioxidant enzyme activity. Hormonal treatment did not change survival during ventilation. The average airspace volume increased in Dex-treated CDH pups after ventilation, with a small synergistic effect after addition of TRH. On the basis of our findings, we speculate that prenatal administration of Dex is the best choice to improve lung maturity and airspace volume in CDH patients.
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PMID:Prenatal hormones alter antioxidant enzymes and lung histology in rats with congenital diaphragmatic hernia. 922 4


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