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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-1 has been shown to prolong the survival of rats exposed to lethal concentrations of oxygen. This oxygen tolerance has been attributed by some workers to an increase of manganese superoxide dismutase. We report here that the administration of interleukin-1 to male adult rats results in (i) significant decrease of pulmonary cytochrome P450 at 24 and 72 hours, (ii) decrease of P450 IIB1 mRNA at 24 and 72 hours and (iii) significant decrease of superoxide anion generation from pulmonary microsomes isolated from treated rats. To the best of our knowledge, this is the first report to demonstrate these effects of interleukin-1 on pulmonary P450 and its oxidase activity (O2- generation). On the basis of these results and several earlier reports in which various P450 depressants have been shown to depress superoxide production from microsomes and to prolong the lives of rodents in hyperoxia, we conclude that oxygen tolerance induced by interleukin-1 administration is likewise mediated, at least in part, by reduced generation of superoxide anion from cytochrome P450 monooxygenase system.
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PMID:Suppressive effect of interleukin-1 on pulmonary cytochrome P450 and superoxide anion production. 132 Aug 74

The lung activity of the antioxidant enzymes (AOEs) copper, zinc superoxide dismutase (Cu,Zn SOD), catalase (CAT), and glutathione peroxidase (GP), but not manganese superoxide dismutase (Mn SOD), increases in rats during late gestation; the concentrations of Cu,Zn SOD mRNA and CAT mRNA also rise. During early postnatal exposure to > 95% O2, the lung activity of Cu,Zn SOD, CAT, and GP increases. We now show 1) the lung concentration of Mn SOD mRNA and GP mRNA does not increase in late gestation; 2) Mn SOD activity and the concentration of its mRNA and of GP mRNA increase during exposure of neonatal rats to > 95% O2; and 3) as previously shown for CAT mRNA, the increase in lung concentration of the mRNAs for Cu,Zn SOD, Mn SOD, and GP during early postnatal hyperoxia occurs with a 70-80% prolongation of the half-life of these mRNAs. We conclude that 1) in late gestation the level at which lung AOE gene expression is regulated differs among the enzymes, 2) the level at which lung AOE gene expression is regulated shortly after birth in response to > 95% O2 is uniform among the enzymes, and 3) the lung's AOE response to neonatal hyperoxia is not merely a step-up of its prenatal regulation but involves different regulatory mechanisms based on increased stability of AOE mRNAs.
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PMID:Rat lung antioxidant enzymes: differences in perinatal gene expression and regulation. 141 24

Replacement of media in cell cultures during exposure to hyperoxia was found to alter oxygen toxicity. Following 100 hr of exposure to 95% or 80% O2, the surviving fraction (SF) of Chinese hamster fibroblasts, as assayed by clonogenicity, was less than 1 x 10(-3) when the culture media was replaced only at the onset of the O2 exposure. Media replacement every 24 hr throughout the hyperoxic exposure resulted in SFs of 1.7 x 10(-1) (95% O2) and 1.9 x 10(-1) (80% O2) at 95 hr. Cellular resistance to and metabolism of 4-hydroxy-2-nonenal (4HNE), a cytotoxic byproduct of lipid peroxidation, was examined in cells 24 hr following exposure to 80% O2 for 144 hr with media replacement. These O2-exposed cells were resistant to 4HNE, requiring 2.6 times as long in 80 microM 4HNE to reach 30% survival as compared to density-matched normoxia control. Furthermore, during 40 and 60 min of exposure to 4HNE, the O2-preexposed cells metabolized greater quantities of 4HNE (fmole/cell) relative to control. The activity of glutathione S-transferase (GST), an enzyme believed to be involved with the detoxification of 4HNE, was significantly increased in the O2-preexposed cells compared with controls. Catalase activity was significantly increased, but no change was found in total glutathione content, glutathione peroxidase, manganese superoxide dismutase, and copper-zinc superoxide dismutase activities at the time of 4HNE treatment in the O2-preexposed cells relative to density-matched control. The results demonstrate that in vitro tolerance to the cytotoxic effects of hyperoxia can be achieved through media replacement during O2 exposure. Tolerance to oxygen toxicity conferred resistance to the cytotoxic effects of 4HNE, possibly through GST-catalyzed detoxification. These results provide further support for the hypothesis that toxic aldehydic byproducts of lipid peroxidation contribute to hyperoxic injury.
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PMID:Replacement of media in cell culture alters oxygen toxicity: possible role of lipid aldehydes and glutathione transferase in oxygen toxicity. 206 63

We have demonstrated a dramatic induction of manganese superoxide dismutase (Mn-SOD) mRNA levels in response to lipopolysaccharide (LPS), interleukin-1, and tumor necrosis factor in pulmonary epithelial cells. These stimuli had no effect on the corresponding mRNA levels for the copper/zinc (Cu/Zn)-SOD. Identical treatments of pulmonary fibroblast cells with LPS showed only minor changes in the Mn-SOD mRNA levels demonstrating a cell type-specific effect for this acute inflammatory mediator. Furthermore, we have shown that hyperoxia has no effect within 24 h on Mn-or Cu/Zn-SOD mRNA levels in either fibroblasts or epithelial cells. The induction of Mn-SOD mRNA levels by LPS is completely inhibited by actinomycin. Treatment of cells with cycloheximide causes an induction equal to that for LPS, whereas co-treatment with cycloheximide and LPS resulted in a "super induction." This data is strongly suggestive of an important role for the Mn-SOD in the acute inflammatory response.
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PMID:Regulation of manganese superoxide dismutase by lipopolysaccharide, interleukin-1, and tumor necrosis factor. Role in the acute inflammatory response. 240 41

The importance of respiratory chain activity in the induction of manganese superoxide dismutase biosynthesis was examined in the yeast Saccharomyces cerevisiae by immunological measurement of the level of manganese superoxide dismutase and comparison with copper/zinc superoxide dismutase and two subunits of respiratory chain proteins, cytochrome c1 and core 2, under conditions of growth in which respiratory chain activity was varied. Oxygen consumption by the yeast was also monitored during growth. These comparative studies indicated that under normoxic conditions, glucose repression of the respiratory chain subunits resulted in a parallel repression of the level of manganese superoxide dismutase protein. The increase in the protein levels of manganese superoxide dismutase and core 2 protein under derepressing growth conditions reflected an increase in the level of the mRNA for each protein; thus regulation is, at least in part, at the level of transcription. The following observations support the conclusion that under normoxic conditions manganese superoxide dismutase biosynthesis is primarily regulated by the same means as the respiratory chain components; that is, by glucose (catabolite) repression rather than by oxygen metabolites. 1) When yeast cells were transferred from repressing to derepressing growth conditions in normoxia, manganese superoxide dismutase biosynthesis increased at a rate parallel to that of core 2, and occurred approximately 5 h in advance of increased oxygen consumption by the yeast. 2) When an important site of mitochondrial superoxide radical generation, the cytochrome bc1 complex, was inactivated by deletion of the gene coding for one of its subunits, the level of manganese superoxide dismutase protein was not changed in the mutant compared with the parental strain. However, regulation of manganese superoxide dismutase can be separated from regulation of the respiratory chain proteins in certain instances. During the transition from the logarithmic growth phase to the stationary phase in non-fermentable carbon sources, the level of manganese superoxide dismutase decreased by approximately 50%, whereas the levels of cytochrome c1 and core 2 remained unchanged. Furthermore, yeast grown in hyperoxia of 70-80% oxygen utilizing either repressing or depressing carbon sources, contained significantly higher levels of manganese superoxide dismutase and copper/zinc superoxide dismutase compared to yeast grown in normoxia, whereas the levels of respiratory chain proteins were not affected by hyperoxia.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Regulation of manganese superoxide dismutase in Saccharomyces cerevisiae. The role of respiratory chain activity. 283 36

In this study, we have used the rat model of hyperoxia to examine the molecular responses to oxidative stress in lung. We show that in addition to the antioxidant enzyme manganese superoxide dismutase, expression of a variety of stress-responsive genes including heme oxygenase-1, c-fos, c-jun, CAAT-enhancer binding protein (C/EBP)-beta, and C/EBP-delta were increased after hyperoxia. Increased c-fos, c-jun, C/EBP-beta, and C/EBP-delta mRNA expression was correlated with increased DNA binding activity of the transcription factor complexes activator protein 1 and C/EBP in tissue lysates. Because oxidative damage plays an important role in the aging process and little is known about the susceptibility of aged rats to hyperoxia, we also examined the relative tolerance of old rats to hyperoxia. Surprisingly, we observed that aged rats exhibit greater tolerance to hyperoxic stress than young rats. Old rats exhibited decreased arterial oxygen tension when compared to young rats after hyperoxia exposure. This increased tolerance coincided with decreased albumin levels in bronchoalveolar lavage and the delayed onset of activation of transcription factors and expression of oxidative stress-inducible genes in old rats. Transcription factor and stress-response gene activation may serve as useful molecular markers for oxidant lung injury.
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PMID:Molecular responses to hyperoxia in vivo: relationship to increased tolerance in aged rats. 759 40

Leukemia inhibitory factor (LIF) and tumor necrosis factor (TNF) have been shown to protect animals from radiation, hyperoxia, and endotoxic shock. TNF is also known to induce the expression of manganese superoxide dismutase (MnSOD) in vitro and in vivo. We therefore examined the effects of these cytokines on reperfusion injury in the isolated rabbit heart model. Rabbits were injected intravenously with 10 micrograms of either human TNF-alpha or lymphotoxin (TNF-beta), or murine TNF-alpha or murine LIF dissolved in saline. Control animals were injected with an equal volume of saline. After 24 h, hearts were isolated and perfused. Following an equilibration period, the hearts were subjected to 1 h ischemia and 1 h of reperfusion. All treated groups showed significant increases in percent recovery of developed tension (% preischemic) when compared to saline-treated control hearts. In addition there were significant decreases in lactate dehydrogenase release (LDH), accumulation of thiobarbituric acid reactive substances (TBARS), and accumulation of carbonyl proteins. These results correlate with increases in myocardial MnSOD activity. Thus, the protection from myocardial reperfusion injury seen in the pretreated group may be due to a mechanism that involves the induction of MnSOD.
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PMID:Leukemia inhibitory factor and tumor necrosis factor induce manganese superoxide dismutase and protect rabbit hearts from reperfusion injury. 776 Mar 46

The significance of manganese superoxide dismutase (MnSOD) induction in cells and tissues during oxidant stress is still poorly understood. In this study, transformed human bronchial epithelial cells (BEAS 2B) were treated with interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), or with combination of these cytokines (10 ng/ml concentrations) for 48 or 72 h and exposed to selected oxidants. TNF-alpha and IFN-gamma + TNF-alpha combination resulted in a marked increase of MnSOD protein and MnSOD activity. When cells pretreated with the cytokines were exposed to hyperoxia (95% O2, 72 h), menadione (5-50 microM, 4 h), or H2O2 (0.5 and 5 mM, 4 h), in all cases IFN-gamma and TNF-alpha enhanced oxidant-related cell injury. The effect was most significant with cells pretreated with a combination of IFN-gamma and TNF-alpha. Antioxidant enzymes such as total SOD, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase did not change significantly during the cytokine treatment. Catalase activity was not changed by IFN-gamma or TNF-alpha but it decreased significantly (34%) in IFN-gamma + TNF-alpha-treated cells. Free radical generation was not changed by these cytokines in acute (30 min) experimental conditions or after 48-h treatment. These results suggest that cytokine-induced MnSOD does not protect bronchial epithelial cells against endogenously or exogenously generated oxidants in vitro. In fact, cells that contained the highest MnSOD activity were the most sensitive to subsequent oxidant damage.
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PMID:Mitochondrial superoxide dismutase induction does not protect epithelial cells during oxidant exposure in vitro. 784 Feb 31

We have analyzed the magnitude and uniformity of the expression of manganese superoxide dismutase (Mn SOD) protein in alveolar type II cells of rats exposed to hyperoxia using quantitative colloidal gold immunocytochemistry and morphometric techniques. Sprague-Dawley rats were exposed continuously to normal air or to 85% oxygen for 7 and 14 days. The lungs were fixed by intratracheal instillation of a paraformaldehyde-glutaraldehyde fixative. Lung samples were dehydrated in ethanol and embedded in LR-White. Thin sections for electron microscopy were labeled with anti-rat Mn SOD rabbit antiserum followed by protein-A gold. The labeling density (gold particles/micron 2) over subcellular compartments was determined, and relative organelle volumes were measured using a random point overlay. The results confirm that alveolar type II cells are a locus of Mn SOD response in the lungs of hyperoxic rats and contribute to this response through a combination of changes: an increase of Mn SOD concentration in the mitochondrial matrix, an increase of mitochondrial volume per cell, and type II cell hyperplasia.
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PMID:Quantitative immunocytochemical analysis of Mn SOD in alveolar type II cells of the hyperoxic rat. 794 50

In evaluating the relative expression of copper-zinc and manganese superoxide dismutase (CuZnSOD and MnSOD) in vivo in states like Down syndrome in which one dismutase is present at increased levels, we measured activities of both enzymes, in tissues of control and transgenic mice constitutively expressing increased levels of CuZnSOD, during exposure to normal and elevated oxygen tensions. Using SOD gel electrophoresis assay, CuZnSOD and MnSOD activities of brain, lung, heart, kidney, and liver from mice exposed to either normal (21%) or elevated (> 99% oxygen, 630 torr) oxygen tensions for 120 h were compared. Whereas CuZnSOD activity was elevated in tissues of transgenic relative to control mice under both normoxic or hyperoxic conditions, MnSOD activities in organs of transgenic mice were remarkably similar to those of controls under both conditions. To confirm the accuracy of this method in quantitating MnSOD relative to CuZnSOD expression, two other methods were utilized. In lung, which is the organ exposed to the highest oxygen tension during ambient hyperoxia, a sensitive, specific ELISA for MnSOD was used. Again, MnSOD protein was not different in transgenic relative to control mice during exposure to air or hyperoxia. In addition, lung MnSOD protein was not changed significantly by exposure to hyperoxia in either group. In kidney, a mitochondrion-rich organ, SOD assay, before and after inactivation of CuZnSOD with diethyldithiocarbamate, was used. MnSOD activity was not different in organs from air-exposed transgenic relative to control mice. The data indicated that expression of MnSOD in vivo was not affected by overexpression of the CuZnSOD and, therefore, the two enzymes are probably regulated independently.
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PMID:Expression of manganese superoxide dismutase is not altered in transgenic mice with elevated level of copper-zinc superoxide dismutase. 813 89


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