Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04179 (MnSOD)
 2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Werner's syndrome is often regarded as a segmental progeroid syndrome. It has been suggested that free radical damage involving oxygen contributes to aging. Furthermore, lymphocytes from Werner's syndrome patients show in vitro increased chromosome breakage and are protected by exogenous superoxide dismutase and catalase. We prepared erythrocytes and lymphocytes from three patients with Werner's syndrome and determined four important enzymes protecting against oxygen toxicity; CuZn superoxide dismutase, Mn superoxide dismutase, catalase and glutathione peroxidase. All enzymic activities were found to be normal.
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PMID:Normal CuZn superoxide dismutase, Mn superoxide dismutase, catalase and glutathione peroxidase in Werner's syndrome. 725 70

The neuronal ceroid-lipofuscinoses are characterized by a widespread deposit in the body of pigments believed to be end products of lipid peroxidation damaged organelles. CuZn superoxide dismutase, Mn superoxide dismutase, catalase and glutathione peroxidase, enzymes which conceivably might protect against lipid peroxidation, were investigated in blood cells from patients afflicted with infantile, late infantile and juvenile neuronal ceroid-lipofuscinosis. In some cases the enzymic activities were slightly lower than the activities of the controls, but no deficiencies which might be of etiolgical importance were revealed.
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PMID:Superoxide dismutase, catalase and glutathione peroxidase in infantile, late infantile and juvenile neuronal ceroid-lipofuscinosis. 729 87

To determine how lipid peroxides and free radical scavengers are changed in the brain of hyper- or hypothyroid rats, we examined the behavior of lipid peroxide and free radical scavengers in the cerebral cortex of aged (1.5 years old) rats that had been made hyper- or hypothyroid by the administration of thyroxine or methimazol for 4 weeks. Concentrations of catalase, Mn-superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) were increased in hyperthyroid rats compared with euthyroid rats. Concentrations of total SOD, Cu,Zn-SOD and GSH-PX were increased but that of Mn-SOD was decreased in hypothyroid animals. There were no differences among hyperthyroid, hypothyroid and euthyroid rats in the levels of coenzymes 9 or 10. The concentration of lipid peroxides, determined indirectly by the measurement of thiobarbituric acid reactants, was decreased in hyperthyroid rats but not in hypothyroid rats when compared with euthyroid animals. These findings suggest that free radicals and lipid peroxides are scavenged to compensate for the changes induced by hyper- or hypothyroidism.
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PMID:Changes in lipid peroxidation and free radical scavengers in the brain of hyper- and hypothyroid aged rats. 749 May 66

Studies have implicated active oxygen species (AOS) in the pathogenesis of various lung diseases. Many chemical and physical agents in the environment are potent generators of AOS, including ozone, hyperoxia, mineral dusts, paraquat, etc. These agents produce AOS by different mechanisms, but frequently the lung is the primary target of toxicity, and exposure results in damage to lung tissue to varying degrees. The lung has developed defenses to AOS-mediated damage, which include antioxidant enzymes, the superoxide dismutases [copper-zinc (CuZnSOD) and manganese-containing (MnSOD)], catalase, and glutathione peroxidase (GPX). In this review, antioxidant defenses to environmental stresses in the lung as well as in isolated pulmonary cells following exposure to a number of different oxidants, are summarized. Each oxidant appears to induce a different pattern of antioxidant enzyme response in the lung, although some common trends, i.e., induction of MnSOD following oxidants inducing inflammation or pulmonary fibrosis, in responses to oxidants occur. Responses may vary between the different cell types in the lung as a function of cell-cycle or other factors. Increases in MnSOD mRNA or immunoreactive protein in response to certain oxidants may serve as a biomarker of AOS-mediated damage in the lung.
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PMID:Regulation of antioxidant enzymes in lung after oxidant injury. 752 4

During radiotherapy of thoracic tumors, the heart is often included in the primary treatment volume, and chronic impairment of myocardial function occurs. The cellular biomolecules are altered directly by radiation or damaged indirectly by free radical production. The purpose of this investigation was to evaluate the biochemical and functional responses of the rat heart to a single high dose of radiation. The effect of 20 Gy local X irradiation was determined in the heart of Wistar rats under general anesthesia. Mechanical performances were measured in vitro using an isolated perfused working heart model, and cardiac antioxidant defenses were also evaluated. Hearts were studied at 1 and 4 months after irradiation. This single dose of radiation induced a marked drop in the mechanical activity of the rat heart: aortic output was significantly reduced (18% less than control values) at 1 month postirradiation and remained depressed for the rest of the experimental period (21% less than control 4 months after treatment). This suggests the development of myocardial failure after irradiation. The decline of functional parameters was associated with changes in antioxidant defenses. The decrease in cardiac levels of vitamin E (-30%) was associated with an increase in the levels of Mn-SOD and glutathione peroxidase (+45.5% and +32%, respectively, at 4 months postirradiation). However, cardiac vitamin C and catalase levels remained constant. Since these antioxidant defenses were activated relatively long after irradiation, it is suggested that this was probably due to the production of free radical species associated with the development of inflammation.
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PMID:Effect of in vivo heart irradiation on the development of antioxidant defenses and cardiac functions in the rat. 756 73

Preimplantation embryos from a variety of mammalian species contrast markedly in their response to culture in vitro. Murine preimplantation embryos display a wider tolerance than other mammalian species to culture environments, and this has contributed to the development of several effective defined culture media. Embryo coculture on somatic cells remains the most effective method of supporting reasonable rates of bovine preimplantation development in vitro. The patterns of gene expression for several antioxidant enzymes during preimplantation murine and bovine development were examined by use of the reverse transcription-polymerase chain reaction technique to determine whether the differential developmental capacity of mammalian preimplantation embryos in culture may reflect variations in the patterns of expression for a series of antioxidant enzymes. Transcripts for catalase, CuZn-containing superoxide dismutase (CuZn-SOD), Mn-SOD, glutathione peroxidase (GPX), and glutamylcysteine synthetase (GCS) were detected in mouse embryos at all stages of development regardless of in vivo or in vitro development. Preimplantation cow embryos produced by in vitro procedures expressed mRNAs for catalase, CuZn-SOD and GPX, whereas transcripts for Mn-SOD were not detected at any stage. GCS transcripts, although present in stages up to the morula, were not detected in cow blastocysts. Analysis of antioxidant gene expression in both bovine primary oviductal cell monolayer cultures and nonattached, ciliated oviductal cell vesicle cultures revealed a constitutive pattern of expression of all five enzymes for the 8-day culture interval. These experiments suggest that differences in gene expression may contribute to the variation in the ability of embryos to develop in vitro with respect to levels of oxygen and dependence on coculture.
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PMID:Expression of genes encoding antioxidant enzymes in preimplantation mouse and cow embryos and primary bovine oviduct cultures employed for embryo coculture. 757 76

An H2O2-resistant variant (OC14) of the HA1 Chinese hamster fibroblast cell line, which demonstrates cross resistance to 95% O2 and a 2-fold increase in total glutathione content, was utilized to investigate mechanisms responsible for cellular resistance to H2O2- and O2-toxicity. OC14 and HA1 cells were pretreated with buthionine sulfoximine (BSO) to deplete total cellular glutathione. Following BSO pretreatment, cells were either placed in 250 microM BSO to maintain the glutathione depleted condition and challenged with 95% O2, or challenged with hydrogen peroxide in the absence of BSO. Total glutathione and the activities of CuZn superoxide dismutase, Mn superoxide dismutase, catalase, glutathione peroxidase, and glutathione transferase were evaluated immediately following the BSO pretreatment as well as following 39 to 42 hr of exposure to 250 microM BSO. BSO treatment did not cause significant decreases in any cellular antioxidant tested, except total glutathione. Glutathione depletion resulted in significant (P < 0.05) sensitization to O2-toxicity and H2O2-toxicity in both cell lines at every time point tested. However, glutathione depletion did not completely abolish the resistance to either O2- or H2O2-toxicity demonstrated by OC14 cells, relative to HA1 cells. Also, glutathione depletion did not effect the ability of OC14 cells to metabolize extracellular H2O2. These data indicate that glutathione dependent processes significantly contribute to cellular resistance to acute H2O2- and O2-toxicity, but are not the only determinants of resistance in cell lines. The contribution of aldehydes formed by lipid peroxidation in mechanisms involved with the sensitization to O2-toxicity in glutathione depleted cells was tested by measuring the lipid peroxidation byproduct, 4-hydroxy-2-nonenal (4HNE), bound in Schiff-base linkages or in its free form in cell homogenates at 49 hr of 95% O2-exposure. No significant increase in 4HNE was detected in glutathione depleted cells relative to glutathione competent cells, indicating that glutathione depletion does not sensitize these cells to O2-toxicity by altering the intracellular accumulation of free or Schiff-base bound 4HNE.
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PMID:Contribution of increased glutathione content to mechanisms of oxidative stress resistance in hydrogen peroxide resistant hamster fibroblasts. 759 39

Premature rabbits, unlike full-term rabbits, are unable to mount a protective increase in pulmonary antioxidant enzyme (AOE) activities in response to 48 h of hyperoxic exposure and demonstrate increased pulmonary O2 toxicity compared with full-term rabbits. To examine AOE gene expression of CuZn superoxide dismutase (SOD), Mn SOD, catalase, and glutathione peroxidase in preterm versus term rabbits in response to hyperoxia, 29.5 d preterm rabbits (delivered by hysterotomy) and term rabbits (spontaneously vaginally delivered) were exposed to 48 h of > 90% O2 or room air. Preterm rabbits had a significant increase in CuZn SOD mRNA without corresponding AOE activity increases, suggesting translational/posttranslational inhibition. In full-term rabbits, the magnitude of lung AOE mRNA changes was associated with concordant magnitude changes in activities of CuZn SOD, Mn SOD, and catalase, suggesting pretranslational regulation of AOE gene expression; glutathione peroxidase, however, appears to be regulated translationally/posttranslationally. To investigate potential pharmacologic means of overcoming the susceptibility of the preterm rabbit to O2 toxicity, 29.5 d preterm rabbits received 20-40 micrograms/kg of Salmonella typhimurium endotoxin or diluent S.C. (after birth and at 24 h); in separate experiments, pregnant rabbits received intramuscular injections of dexamethasone (0.01-0.05 mg/kg) or saline on gestational d 27.5 and 28.5 and underwent hysterotomy at 29.5 d.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Failure of premature rabbits to increase lung antioxidant enzyme activities after hyperoxic exposure: antioxidant enzyme gene expression and pharmacologic intervention with endotoxin and dexamethasone. 759 87

We report a transient adaptation to the oxidative stress of hydrogen peroxide (H2O2) exposure in several mammalian cell lines: Chinese hamster ovary fibroblast (CHO) cells, HA-1 cells (a defined CHO subclone), C3H 10T1/2 cells (embryonic mouse fibroblasts), V79 cells (Chinese hamster lung fibroblasts), and Clone 9 liver cells (rat liver epithelial cells). Up to 40-fold adaptive increases in resistance to H2O2 challenge occurred following pretreatment with relatively low H2O2 "priming" doses, from as little as 1.9% cell viability for untreated cells to as much as 76.5% viability for H2O2 pretreated cells. Detailed studies with HA-1 cells revealed the following pattern of responses to H2O2: very low H2O2 concentrations of 0.1 to 0.5 mumol/10(7) cells (3 to 15 microM) stimulated cell growth by 25 to 45%; low H2O2 concentrations of 2-5 mumol/10(7) cells (120 to 150 microM) induced a temporary growth-arrest, a lengthening of cell cycle from 18 h to approximately 26 h, and marked adaptive increases in H2O2 resistance; intermediate H2O2 concentrations of 9 to 14 mumol/10(7) cells (250 to 400 microM) caused permanent growth-arrest (i.e., permanent loss of replicative or divisional competence) with no evidence of necrosis; high H2O2 concentrations of 30 mumol/10(7) cells or greater (> or = 1 mM) caused an apoptotic-like necrotic cell death and destruction. The adaptive response to low H2O2 concentrations of 2-5 mumol/10(7) (120 to 150 microM) was maximal 18 h after pretreatment of HA-1 cells, declined thereafter toward baseline sensitivity, and was observed with both 7-day fix and stain procedures and clonogenic viability assays. Transient adaptation following H2O2 pretreatment of 4.15 mumol/10(7) (150 microM) involved the de novo synthesis of at least 20 proteins and was blocked by the translation inhibitor, cycloheximide. During the 18-h adaptation in HA-1 cells proteins were synthesized in three phases; early (0-4 h), middle (4-8 h), and late (8-15 h). No H2O2 response proteins were synthesized beyond 18 h after pretreatment, by which time adaptation had already maximized. Selective translational inhibition of the early, middle, or late proteins revealed that all three sets were necessary for a maximal adaptive increase in H2O2 resistance. Northern blot and enzyme activity analyses revealed no significant increases in transcription or translation of the classical antioxidant enzymes catalase, glutathione peroxidase, phospholipid hydroperoxide glutathione peroxidase, Cu, Zn superoxide dismutase, or Mn superoxide dismutase in H2O2-adapted HA-1 cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Transient adaptation of oxidative stress in mammalian cells. 772 66

Exposure to hyperoxia causes alveolar macrophage (AM) injury. The present study investigates the roles of intracellular antioxidant enzymes and of glutathione in the protection of AMs against hyperoxia in a biphasic cell culture system in aerobiosis. The effect of normoxia or hyperoxia on the integrity of AMs was related to indices of cell injury (ATP cell content and lactate dehydrogenase release into culture medium) and cell mass (protein content of AMs). Antioxidant activities were measured in guinea-pig AMs exposed to 95% O2 or to normoxia (control cells) for 3 days. A 3-day AM culture in normoxia showed a significant decrease in protein and catalase, whereas ATP cell content, superoxide dismutase (SOD) (both Cu,Zn-SOD and Mn-SOD) and glutathione peroxidase (GPx) activities significantly increased. The content of reduced glutathione (GSH) did not change. Using the ATP content in AMs expressed as a cell injury index (CII), AM injury increased with increasing O2 exposure time (1 day: 13 +/- 4.4%; 2 days: 34 +/- 3.8%; 3 days: 40 +/- 4.1%; 4 days: 55 +/- 7.3%; 6 days: 87.5 +/- 5.4%). Exposure to 95% O2 for 3 days was associated with a significant decrease in ATP cell content, protein, catalase and GSH to the total glutathione ratio, whereas SOD, GSH and total glutathione did not change significantly. The GPx activities increased significantly. There was no significant correlation between the AM CII and SOD or GPx content. In contrast, a significant correlation was observed between hyperoxia-induced AM CII and catalase content (r = 0.71) and glutathione content (r = 0.71).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relationship between oxygen-induced alveolar macrophage injury and cell antioxidant defence. 774 27


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