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)

Fetal rat lung fibroblasts were cultured in a gas phase of 20% O2, 5% CO2 (PO2 measured, 150 Torr) or 2% oxygen, 5% CO2 (PO2 measured, 25 Torr) with or without 100 nM dexamethasone (Dex). Superoxide dismutase (SOD) activity per cell increased spontaneously during 4 days of incubation at both PO2, but catalase (CAT) activity tended to fall during this time and glutathione peroxidase (GPx) activity showed no consistent trend during this interval. Cells cultured at a low PO2 had a lower protein content and SOD activity compared with air controls. Dex inhibited cell proliferation and enhanced intracellular accumulation of protein at the low PO2 but prevented the increase in protein content without affecting cell multiplication at a PO2 of 150 Torr. SOD activity per cell was enhanced by Dex at a low PO2 but reduced in 20% O2, 5% CO2. An increase in CAT and GPx activity per cell resulted on exposing fibroblasts to Dex in the presence of low PO2. These results show that Dex affects the growth and antioxidant enzyme activity of fetal lung fibroblasts, and this action of Dex can be modulated by changing the ambient PO2.
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PMID:PO2-dexamethasone interactions in fibroblast growth and antioxidant enzyme activity. 356 58

Total glutathione levels and the activity of enzymes associated with antioxidant protection in neonatal lung are increased in response to hyperoxia. Glutathione levels in developing rat lung decreased from 24 nmol/mg protein on day 19 of gestation to approximately 12 nmol/mg protein at birth. The initial decrease in glutathione may be due to emergence of other antioxidant systems. Newborn rats placed in 100% oxygen showed a rapid and sustained increase in total glutathione levels which was primarily due to an increase in reduced glutathione. Explants obtained from 16-wk gestation human fetal lung or from 17- to 18-day fetal rat lung also showed increased total and reduced glutathione when cultured in 95% oxygen, 5% CO2 as compared with explants cultured in room air. Type II cells isolated from neonatal rats maintained in oxygen for 6 days also showed glutathione levels twice those found in cells isolated from animals in room air. The activity of antioxidant enzymes (glucose-6-phosphate dehydrogenase, glutathione peroxidase, glutathione reductase) was increased in lungs of newborn rats exposed to 100% oxygen either at birth or 2 days of age. Antioxidant enzyme activity of lung explants cultured in 95% oxygen, 5% CO2 was also higher than in explants maintained in room air. These results suggest that the increases in glutathione and of antioxidant enzymes in vivo and in vitro are a direct effect of oxygen exposure in lung and that the increase of both glutathione and antioxidant enzyme activity is intrinsic to the lung cell itself. It is likely that increases in glutathione in lung represent an important protective mechanism against oxidant injury.
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PMID:The responses of glutathione and antioxidant enzymes to hyperoxia in developing lung. 403 84

The effect of a 6-kDa thymic peptide (TP) on the oxidative burst of the murine macrophage cell line J774 was determined. TP was incubated with J774 cells at 37 degrees C and 5% CO2 for 18 h, oxidative burst was triggered by zymosan, and chemiluminescence was amplified by luminol and measured in an automated luminometer. TP exhibited a concentration-dependent suppression of oxidative burst. To study the mechanisms involved in TP's suppression of oxidative burst, its effect on the glutathione redox cycle and antioxidant enzymes was investigated. J774 cells were incubated with varying concentrations of TP for 18 h, washed, resuspended in phosphate-buffered saline, and sonicated to obtain cell lysate. Biochemical assays were performed with the lysate. TP was shown to increase the level of glutathione, and activities of glutathione-peroxidase and glutathione-reductase, indicating its ability to modulate the glutathione redox cycle. The activity of antioxidant enzyme superoxide dismutase was enhanced significantly by TP treatment while catalase activity remained unaffected. These results suggest that TP possesses an antioxidant property and therefore may be involved in the regulation of free radical mediated reactions.
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PMID:Thymic peptide modulates glutathione redox cycle and antioxidant enzymes in macrophages. 814 20

It has been suggested that oxidative processes are involved in a variety of pathological conditions, notably ischemia-reperfusion injury. Moreover, anesthetics appear to exert differential effects on the severity of such injury, these being unlikely wholly attributable to their differential effects on cardiovascular or microcirculatory status. It is possible that these variable effects of anesthetics on this type of injury may be due, at least in part, to changes in the production of free radicals and/or in their detoxification by endogenous antioxidant enzymes. We have attempted to explore the latter possibility by measuring activities of catalase, superoxide dismutase (SOD), glutathione peroxidase (GPX) and glutathione reductase in normal heart tissue and red cells obtained from rats anesthetized using a variety of agents (CO2, halothane, pentobarbital or ether). For comparison, analyses were also performed on tissues from unanesthetized animals rendered unconscious by stunning prior to sacrifice. Results indicated that myocardial SOD activity was significantly greater in halothane-anesthetized as compared with CO2-anesthetized animals. Red cell SOD activities did not show such differences. However, red cell GPX activity was found to be greater in halothane-anesthetized than in pentobarbital-anesthetized rats. In general, however, antioxidant enzyme activities measured ex vivo were minimally affected by the use of anesthetics prior to euthanasia. Our findings, therefore, do not support the proposal that the influence of anesthetics on the course of ischemia-reperfusion injury involves effects at the level of enzymatic antioxidant components.
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PMID:Effects of various anesthetic regimens on tissue antioxidant enzyme activities. 816 73

Epidermal growth factor (EGF) has been shown to accelerate fetal lung maturation in rabbits, lambs, and rhesus monkeys in vivo and increase surfactant synthesis in vitro. Its effect on the maturation of the lung antioxidant enzyme system, however, is unknown. We studied the effect of EGF (10 nM) on 19-d fetal rat lung explant cultures in serum-free medium in air/5% CO2 or > 90% O2/5% CO2 compared with similarly grown control cultures in air or hyperoxia at 72 h. Fetal lung activities of superoxide dismutase and catalase were unchanged by EGF in air, whereas glutathione peroxidase activity was significantly decreased (p < 0.05 versus air control). However, in hyperoxia, EGF-treated fetal lung cultures had significantly elevated superoxide dismutase and catalase activities (p < 0.01) versus O2-exposed controls, and glutathione peroxidase activity similar to that of controls. The mRNA levels for all the antioxidant enzymes showed patterns similar to the enzyme activities except in the case of Cu,Zn-superoxide dismutase mRNA, which increased in EGF-air cultures. EGF decreased the rate of 3H-choline incorporation into disaturated phosphatidylcholine in air (p < 0.01 versus air control), but increased disaturated phosphatidylcholine synthesis in response to hyperoxia (p < 0.01 versus O2 control). The histologic appearance of EGF-treated cultures in O2 was superior to that of O2-exposed controls, which showed thickened septal walls, decreased surfactant in the air spaces, and epithelial cell mitochondrial swelling. EGF therefore accelerates antioxidant enzyme and disaturated phosphatidylcholine maturation under hyperoxic conditions and protects fetal rat lung cultures from hyperoxic injury.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Epidermal growth factor increases antioxidant enzyme and surfactant system development during hyperoxia and protects fetal rat lungs in vitro from hyperoxic toxicity. 828 92

Heme oxygenase (HO) is believed to be a potent antioxidant enzyme in the nervous system; it degrades heme from heme-containing proteins, giving rise to carbon monoxide, iron, and biliverdin, which is rapidly reduced to bilirubin. The first identified isoform of the enzyme, HO1, is an inducible heat-shock protein expressed in high levels in peripheral organs and barely detectable under normal conditions in the brain, whereas HO2 is constitutive and most highly concentrated in the brain. Interestingly, although HO2 is constitutively expressed, its activity can be modulated by phosphorylation. We demonstrated that bilirubin, formed from HO2, is neuroprotectant, as neurotoxicity is augmented in neuronal cultures from mice with targeted deletion of HO2 (HO2(-/-)) and reversed by low concentrations of bilirubin. We now show that neural damage following middle cerebral artery occlusion (MCAO) and reperfusion, a model of focal ischemia of vascular stroke, is substantially worsened in HO2(-/-) animals. By contrast, stroke damage is not significantly altered in HO1(-/-) mice, despite their greater debility. Neural damage following intracranial injections of N-methyl-d-aspartate (NMDA) is also accentuated in HO2(-/-) animals. These findings establish HO2 as an endogenous neuroprotective system in the brain whose pharmacologic manipulation may have therapeutic relevance.
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PMID:Heme oxygenase-2 is neuroprotective in cerebral ischemia. 1060 74

Heme, the iron-porphyrin coordination complex, released from the degradation of hemoproteins, is a strong prooxidant. It is enzymatically degraded by heme oxygenase to free iron, carbon monoxide and biliverdin. Biliverdin and its reduced metabolite bilirubin are two potent physiological antioxidants. Here we show a progressive increase of steady-state levels of the mRNA encoding the inducible isoform of this enzyme (heme oxygenase-1) in the rat liver during aging. We had previously reported that aging is associated with increased activation of the nuclear factor kappaB (NFkappaB). We now provide evidence to establish that overexpression of NFkappaB in transfected liver-derived HepG2 cells can cause a marked induction of the endogenous heme oxygenase-1 (HO-1) mRNA and activation of the cotransfected HO-1 gene promoter. Taken together, these results support the conclusion that enhanced oxidative stress during aging is accompanied by compensatory induction of the antioxidant enzyme HO-1 through activation of the NFkappaB pathway.
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PMID:Age-dependent increase of heme oxygenase-1 gene expression in the liver mediated by NFkappaB. 1073 81

Manganese superoxide dismutase (MnSOD) is an antioxidant enzyme that reduces superoxide anion to hydrogen peroxide in cell mitochondria. MnSOD is overexpressed in normal aging brain and in various central nervous system disorders; however, the mechanisms mediating the upregulation of MnSOD under these conditions remain poorly understood. We previously reported that cysteamine (CSH) and other pro-oxidants rapidly induce the heme oxygenase-1 (HO-1) gene in cultured rat astroglia followed by late upregulation of MnSOD in these cells. In the present study, we demonstrate that antecedent upregulation of HO-1 is necessary and sufficient for subsequent induction of the MnSOD gene in neonatal rat astroglia challenged with CSH or dopamine, and in astroglial cultures transiently transfected with full-length human HO-1 cDNA. Treatment with potent antioxidants attenuates MnSOD expression in HO-1-transfected astroglia, strongly suggesting that intracellular oxidative stress signals MnSOD gene induction in these cells. Activation of this HO-1-MnSOD axis may play an important role in the pathogenesis of Alzheimer disease, Parkinson disease and other free radical-related neurodegenerative disorders. In these conditions, compensatory upregulation of MnSOD may protect mitochondria from oxidative damage accruing from heme-derived free iron and carbon monoxide liberated by the activity of HO-1.
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PMID:Role of heme oxygenase-1 in the regulation of manganese superoxide dismutase gene expression in oxidatively-challenged astroglia. 1094 21

Heme oxygenase (HO) is considered to be an antioxidant enzyme that catabolizes heme to produce carbon monoxide (CO) and biliverdin. We determined the expression and distribution of HO-1 and HO-2, two isoenzymes of HO, in the airways of patients with asthma, and determined the effect of inhaled corticosteroid therapy. Immunostaining for both enzymes was widely distributed in the airways' submucosa, particularly in airway epithelium and submucosal macrophages (CD68(+)) as determined by double immunostaining. There was no difference in intensity and extent of staining in biopsies from normal subjects (n = 10) and subjects with asthma (n = 10). Following 1 mo of treatment with inhaled corticosteroids (budesonide 1,600 microg/d), there was no significant change in the expression and distribution of either HO-1 or HO-2 in the airways' submucosa in eight subjects with mild asthma, despite a significant reduction in airway eosinophils and a reduction in bronchial responsiveness to methacholine. Levels of exhaled nitric oxide were significantly reduced, but exhaled CO levels remained unchanged by the treatment. Treatment with a placebo inhaler (n = 8) had no effects on these parameters. Thus, both HO-1 and HO-2 are extensively distributed equally in normal subjects and subjects with asthma, and are not modulated by inhaled corticosteroid therapy in subjects with asthma. HO may be an important endogenous antioxidant enzyme.
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PMID:Expression of heme oxygenase isoenzymes 1 and 2 in normal and asthmatic airways: effect of inhaled corticosteroids. 1106 34

Ginkgo biloba extract (EGb 761) is a standardized extract originating in traditional Chinese medicine. Ginkgo biloba dried leaves have been used for centuries to treat various neurological conditions. The constituents from the extract are likely to have synergistic effects that have been shown to be protective against oxidative stress injury. However, the cellular mechanisms of protection afforded by Ginkgo biloba are still unclear. The cascade leading to neuronal cell death in acute and chronic neurodegenerative conditions, such as cerebral ischemia and Alzheimer's disease, has been postulated to be mediated by free radical damage. We tested the hypothesis that the neuroprotective action of EGb 761 could be due partially to an induction of heme oxygenase I (HO1). We and others have previously reported that modulation of HO total activity may well have direct physiological implications in stroke and in Alzheimer's disease. Heme oxygenase acts as an antioxidant enzyme by degrading heme into iron, carbon monoxide, and biliverdin which is rapidly converted into bilirubin. Through the use of primary neuronal cultures, we demonstrated that EGb 761 induces HO1 in a dose-dependent manner (0, 10, 50, 100 and 500 microg/ml) and time-dependent manner with a maximal induction at 8 hr. We are proposing that several of the protective effects of EGb 761 in ischemia could be mediated through beneficial actions of heme degradation and its metabolites.
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PMID:Induction of heme oxygenase 1 by Ginkgo biloba in neuronal cultures and potential implications in ischemia. 1239 75


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