Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P30044 (antioxidant enzyme)
 8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We carried out a study to relate the effect of the type of dietary fat and ethanol on antioxidant enzyme mRNA levels in liver in the intragastric feeding rat model. Different types of dietary fat were administered [saturated fat (SE), corn oil (CE) and fish oil (FE)] with ethanol to induce varying severities of liver injury. Ethanol-fed rats were pair-fed with dextrose-fed controls that received isocaloric amounts of dextrose. All animals were killed at 1 month and the following studies were carried out: evaluation of severity of pathologic liver injury, mRNA quantitation for catalase, glutathione peroxidase (GPx), and manganese superoxide dismutase (MnSOD), microsomal conjugated dienes, and hydrogen peroxide. SE animals had no liver injury, FE animals had severe liver injury, and CE animals had moderate liver injury. Ethanol induced GPx mRNA in all dietary groups, with the highest levels seen in the FE group. The pattern of catalase mRNA induction was similar to that of GPx mRNA. In contrast, MnSOD mRNA was decreased compared to controls in animals that developed pathologic liver injury, i.e., CE and FE groups. A positive correlation was seen between conjugated diene levels and GPx mRNA (r = 0.88, P < 0.01) and catalase mRNA. The similar slopes for the relationship between conjugated dienes and catalase in the fish oil and non-fish oil groups indicate that the same degree of lipid peroxidation increases catalase mRNA to a greater degree in fish oil-fed rats. A positive correlation was also seen between catalase mRNA and H2O2 (r = 0.95, P < 0.001).
 ...
PMID:Effect of type of dietary fat and ethanol on antioxidant enzyme mRNA induction in rat liver. 761 20

Though bacteria of the radiation-resistant genus Deinococcus have a high resistance to the lethal and mutagenic effects of many DNA-damaging agents, the mechanisms involved in the response of these bacteria to oxidative stress are poorly understood. To investigate antioxidant enzyme responses in Deinococcus spp., the catalase activity produced by these bacteria was measured and the sensitivity of these bacteria to hydrogen peroxide was tested. Deinococcus spp. had higher levels of catalase and were more resistant to hydrogen peroxide than Escherichia coli K12. The high levels of catalase produced by Deinococcus radiodurans were, in part, regulated by growth phase. Cultures of D. radiodurans, when pretreated with sublethal levels of hydrogen peroxide, became relatively resistant to the lethal effects of hydrogen peroxide and exhibited higher levels of catalase than untreated control cultures. These pretreated cells were also resistant to lethality mediated by ultraviolet light and gamma-rays. These results suggest that Deinococcus spp. possess inducible defense mechanism(s) against the deleterious effects of oxidants and ionizing and ultraviolet radiation.
 ...
PMID:Induction of resistance to hydrogen peroxide and radiation in Deinococcus radiodurans. 772 13

Hearts from rats treated with interleukin-1 (IL-1) intraperitoneally developed a rapid (6 h after IL-1), transient increase in neutrophils, tissue hydrogen peroxide (H2O2), and oxidized glutathione (GSSG) levels, and a subsequent (36 h after IL-1) increase in myocardial glucose-6-phosphate dehydrogenase (G6PD) activity and tolerance to ischemia-reperfusion. In the present investigation, we found that rats treated similarly with IL-1 had increased numbers of neutrophils in their kidneys, which were comparable to myocardial neutrophil increases, but did not develop increased renal tissue H2O2 or GSSG levels acutely (6 h after IL-1) or increased G6PD activity or resistance to ischemia-reperfusion injury later (36 h after IL-1). Our findings indicate that IL-1 treatment increased neutrophil accumulation in rat kidneys but did not increase oxidative stress, antioxidant enzyme activity, or resistance to ischemia-reperfusion injury. We conclude that organ-to-organ differences exist with respect to IL-1-induced tolerance.
 ...
PMID:Interleukin-1 treatment increases neutrophils but not antioxidant enzyme activity or resistance to ischemia-reperfusion injury in rat kidneys. 784 98

A 25-kDa antioxidant enzyme that provides protection against oxidation systems capable of generating reactive oxygen and sulfur species has previously been identified. The nature of the oxidant eliminated by, and the physiological source of reducing equivalents for, this enzyme, however, were not known. The 25-kDa enzyme is now shown to be a peroxidase that reduces H2O2 and alkyl hydroperoxides with the use of hydrogens provided by thioredoxin, thioredoxin reductase, and NADPH. This protein is the first peroxidase to be identified that uses thioredoxin as the immediate hydrogen donor and is thus named thioredoxin peroxidase (TPx). TPx exists as a dimer of identical 25-kDa subunits that contain 2 cysteine residues, Cys47 and Cys170. Cys47-SH appears to be the site of oxidation by peroxides, and the oxidized Cys47 probably reacts with Cys170-SH of the other subunit to form an intermolecular disulfide. Mutant TPx proteins lacking either Cys47 or Cys170, therefore, do not exhibit thioredoxin-coupled peroxidase activity. The TPx disulfide is specifically reduced by thioredoxin, but can also be reduced (less effectively) by a small molecular size thiol. The Saccharomyces cerevisiae thioredoxin reductase gene was also cloned and sequenced, and the deduced amino sequence was shown to be 51% identical with that of the Escherichia coli enzyme.
 ...
PMID:Thioredoxin-dependent peroxide reductase from yeast. 796 86

Changes in red blood cell (RBC) lipid peroxidation [measured by malonyl dialdehyde (MDA) concentration], glutathione (GSH) metabolism, antioxidant enzyme activities (catalase, superoxide dismutase, glutathione peroxidase) and haemoglobin (Hb) metabolites (metHb, carboxy Hb) were studied in six children with post-enteropathic (D+) haemolytic uraemic syndrome (HUS) and ten controls. The in vitro effect of hydrogen peroxide [acetylphenylhydrazine (APH) test] on GSH and Hb metabolism was also investigated. MDA levels were significantly higher and the antioxidant enzyme activities were lower in HUS patients than in the controls (P < 0.01). The oxidised glutathione concentration was significantly higher in the patients than in the control children (26.3 +/- 12.6 vs. 10.9 +/- 1.8 nmol/g Hb. Percentage values of carboxy Hb and metHb were also higher in HUS (P < 0.01). Incubation of RBC with APH induced a more pronounced decrease in the concentration of GSH (P < 0.001) and a significant increase (P < 0.01) in the level of metHb and carboxy Hb in the HUS patients. This suggests that there is reduced RBC GSH stability in HUS. Utilisation of GSH and antioxidant enzymes leads to increased Hb oxidation and haemolysis. The oxidative damage may have an important role in the pathogenesis of haemolytic anaemia in HUS.
 ...
PMID:Oxidative damage of red blood cells in haemolytic uraemic syndrome. 814 20

Superoxide dismutase (SOD), which breaks down superoxide to oxygen and hydrogen peroxide, is generally considered an antioxidant enzyme. However, superoxide is a potent reducing agent and as such could affect cellular function by reducing disulfides in important proteins, such as, ionic channels and pumps. In support of this concept, we show that superoxide, generated by two different sources, is able to reduce disulfide bonds in an in vitro model. Depending on the source of superoxide this reduction is accelerated by an unsaturated fatty acid or ferric iron and is inhibited by SOD.
 ...
PMID:Superoxide reduction of a disulfide: a model of intracellular redox modulation? 818 13

This study tested the hypothesis that reactive oxygen intermediates present in unfatigued skeletal muscle act to enhance contractile function. Fiber bundles from rat diaphragm were incubated with exogenous catalase (an antioxidant enzyme that dehydrates hydrogen peroxide to molecular oxygen and water) to decrease the tissue concentration of reactive oxygen intermediates. Catalase (10(3) U/ml) significantly decreased twitch characteristics (time to peak tension, half-relaxation time, peak force, and twitch-to-tetanus force ratio), thereby shifting the force-frequency relationship to the right. Catalase effects were dose dependent. Concentrations of 1 to 10(5) U/ml progressively depressed submaximal (30-Hz) tetanic stress, whereas concentrations > 10(5) U/ml were toxic, inhibiting maximal (200-Hz) tetanic stress (P < 0.0001). Exogenous hydrogen peroxide (10(-4) to 10(-2)M) increased peak twitch stress (P < 0.03) and lengthened both time to peak tension (P < 0.02) and half-relaxation time (P < 0.02). Selective removal of superoxide anion radicals with the use of superoxide dismutase produced dose-dependent contractile inhibition similar to that produced by catalase. We conclude that the reactive oxygen intermediates present in unfatigued skeletal muscle have a positive effect on excitation-contraction coupling and are obligatory for optimal contractile function.
 ...
PMID:Reactive oxygen in skeletal muscle. III. Contractility of unfatigued muscle. 822 15

We quantitated the ability of intratracheally administered liposome-encapsulated antioxidant enzymes to reduce reactive oxygen species injury to the pulmonary microvasculature. Cationic liposomes containing 3,500 U of Cu,Zn superoxide dismutase (Cu,Zn SOD) and 3,124 U of catalase were instilled into rabbits. The animals were killed 2-72 h later and their lungs were removed and perfused with Krebs Ringer with 5% wt/vol of fat-free bovine serum albumin. The pulmonary filtration co-efficient (Kf,c) was measured before and after adding 500 microM xanthine and 5 mU/ml xanthine oxidase (XO) into the lung perfusate. Two hours after a single intratracheal instillation of liposome-entrapped Cu,Zn SOD and catalase, lung antioxidant enzyme activities were 34 and 125% higher than the corresponding control values, remained virtually unchanged for up to 8 h post-instillation, and then decreased, reaching baseline values between 24 and 72 h. Addition of xanthine and XO into the lung perfusate of un-instilled rabbits, or rabbits that received liposomes with inactivated enzymes, caused a 100% increase in Kf,c (control value: 2 +/- 0.12 ml.min-1 x cmH2O-1 per 100 g dry lung weight). On the other hand, Kf,c values of rabbits lungs instilled with liposome-encapsulated active Cu,Zn SOD and catalase and challenged with xanthine and XO 8-24 h later remained at baseline levels. Instillation of liposomes containing either enzyme was equally effective in preventing the increase in Kf,c, indicating that both superoxide anions and hydrogen peroxide were necessary for the initiation of injury. We concluded that intratracheal instillation of liposome-encapsulated antioxidant enzymes caused a transient increase of lung antioxidant enzyme levels which protects the pulmonary microvasculature from free radical-initiated injury.
 ...
PMID:Mitigation of oxidant injury to lung microvasculature by intratracheal instillation of antioxidant enzymes. 823 68

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.
 ...
PMID:On the protective mechanism of the thiol-specific antioxidant enzyme against the oxidative damage of biomacromolecules. 829 8

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.
 ...
PMID:Iron sequestration by macrophages decreases the potential for extracellular hydroxyl radical formation. 838 3


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>