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

CNS oxygen (O2) toxicity is complex, and the etiology of its most severe manifestation, O2 convulsions, is yet to be determined. A role for depletion of the brain GABA pool has been proposed, although recent data have implicated production of reactive O2 species, e.g. H2O2, in this process. We hypothesized that the production of H2O2 and NH3 produced by monoamine oxidase (MAO) would lead to depletion of GABA and production of nitric oxide (NO.) respectively, and thereby enhance CNS O2 toxicity. In this study, rats treated with an MAO inhibitor (pargyline) or a nitric oxide synthase inhibitor (LNNA) were protected against O2-induced convulsions. Selected cerebral amino acids including arginine were measured in control and O2 treated rats (6 ATA, 20 min) with or without drug pretreatment. After O2 exposure, the cerebral pools of glutamate, aspartate, and GABA decreased significantly while glutamine content increased relative to control (P < 0.05). After treatment with either enzyme inhibitor, glutamine, glutamate and aspartate concentrations were maintained near control levels. Remarkably, GABA depletion by O2 was not prevented despite protection from seizures by both pargyline and LNNA. The NO. precursor, arginine, was increased significantly in the brain by toxic O2 exposure, but both pargyline and LNNA inhibited this effect. Simultaneous norepinephrine measurements indicated that its storage substantially decreased during hyperoxia (P < 0.05), but this effect too was blocked by either pargyline or LNNA. These data indicate that protection against O2 by these inhibitors is not related to preservation of the GABA pool. More importantly, O2 dependent norepinephrine metabolism and NO. synthesis appear to be interactive during CNS O2 toxicity.
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PMID:Cerebral amino acid, norepinephrine and nitric oxide metabolism in CNS oxygen toxicity. 846 4

All forms of aerobic life are faced with the threat of oxidation from molecular oxygen (O2) and have evolved antioxidant defenses to cope with this potential problem. However, cellular antioxidants can become overwhelmed by oxidative insults, including supraphysiologic concentrations of O2 (hyperoxia). Oxidative cell injury involves the modification of cellular macromolecules by reactive oxygen intermediates (ROI), often leading to cell death. O2 therapy, which is a widely used component of life-saving intensive care, can cause lung injury. It is generally thought that hyperoxia injures cells by virtue of the accumulation of toxic levels of ROI, including H2O2 and the superoxide anion (O2-), which are not adequately scavenged by endogenous antioxidant defenses. These oxidants are cytotoxic and have been shown to kill cells via apoptosis, or programmed cell death. If hyperoxia-induced cell death is a result of increased ROI, then O2 toxicity should kill cells via apoptosis. We studied cultured epithelial cells in 95% O2 and assayed apoptosis using a DNA-binding fluorescent dye, in situ end-labeling of DNA, and electron microscopy. Using all approaches we found that hyperoxia kills cells via necrosis, not apoptosis. In contrast, lethal concentrations of either H2O2 or O2- cause apoptosis. Paradoxically, apoptosis is a prominent event in the lungs of animals injured by breathing 100% O2. These data indicate that O2 toxicity is somewhat distinct from other forms of oxidative injury and suggest that apoptosis in vivo is not a direct effect of O2.
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PMID:Cellular oxygen toxicity. Oxidant injury without apoptosis. 866 47

The induction of 8-hydroxyguanine (oh8Gua) endonuclease, a DNA repair enzyme for an oxidatively modified guanine, oh8Gua was studied in various growth conditions in Escherichia coli (AB1157). Anaerobically grown E. coli were found to have a very low activity of this enzyme while aerobically grown cells showed activity about 20 times that of the anaerobic level. Under the same condition, superoxide dismutase (SOD) showed about 6-fold increase in activity. A shift in growth conditions from anaerobic to aerobic resulted in rapid induction of this enzyme, and this induction was blocked (but not completely) by chloramphenicol. It is indicated that molecular oxygen is an effective stimulator to the induction of this enzyme and its induction depends partly on protein synthesis. Superoxide-producing compounds such as paraquat and menadione also increased the activity of endonuclease as well as SOD, but H2O2 showed no effect. Thus, superoxides are also implied as a stimulator. In contrast, hyperoxia induced only SOD not the endonuclease. This induction of the endonuclease by hyperoxia was only observed in a SOD-deficient strain (QC774). The aerobic activity of the endonuclease in QC774 was the same as that of wild types (AB1157, GC4468). It is implied that the responsiveness of oh8Gua endonuclease to superoxides is less sensitive than that of SOD. The endonuclease was also induced by a temperature shift from 30 to 43 degrees C and treatment with nalidixic acid. Among the stimuli used, molecular oxygen seems to be most effective for its induction. The inducible nature of this enzyme will serve as an important mechanism for the protection of oxidative DNA damage in the aerobic environment.
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PMID:Induction of E. coli oh8Gua endonuclease by oxidative stress: its significance in aerobic life. 867 25

Heme oxygenase (HO) is the rate-limiting enzyme in the production of bilirubin from heme, and HO-1 is its inducible isoenzyme. In the metabolic pathway of HO a potential oxidant, heme, is degraded, a potential antioxidant, bilirubin, is generated, and a potent sequestering agent of redox active iron, ferritin, is thought to be coinduced. Therefore, the sum of the reactions of HO may be useful in antioxidant defense. To explore the role of HO in protection against oxidative stress, we examined HO-1 expression in Chinese hamster fibroblasts (HA-1) as well as stable hydrogen peroxide (H2O2)-resistant (OC-14) and 95% O2-resistant (O2R95) variant cell lines derived from HA-1, after exposure to 72 h of hyperoxia (95% O2-5% CO2). Total HO activity, HO-1 protein, and HO-1 mRNA steady-state levels were assessed before exposure and daily during exposure to hyperoxia. Controls were exposed to 95% air-5% CO2. Confluent monolayers of O2R95 and OC-14 cells had increased basal immunoreactive HO-1 protein levels relative to HA-1 cells when the cells were grown in normoxia, and O2R95 had higher total basal HO activity. When exposed to hyperoxia for up to 3 days, O2R95 cells, which were resistant to oxygen-induced killing, did not show induction of HO-1 mRNA or increased immunoreactive protein, whereas OC-14 and HA-1, which were relatively more sensitive than O2R95 to oxygen-related cytotoxicity, demonstrated significant increases in HO-1 expression during exposure to hyperoxia. Basal ferritin protein levels were highest in the O2R95 cells, intermediate in OC-14, and lowest in HA-1, but ferritin protein did not increase further, with hyperoxic exposure, in any of the cell lines. We conclude that increased constitutive HO-1 expression is associated with resistance to hyperoxia, whereas induction of HO-1 mRNA is an index of oxidative injury, since it only occurs after cells have sustained cytotoxic injury. We also conclude that increased ferritin expression does not necessarily accompany increased HO-1 expression in oxidant stress. We speculate that HO-1 plays a role in protection against hyperoxic damage.
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PMID:Differences in basal and hyperoxia-associated HO expression in oxidant-resistant hamster fibroblasts. 889 16

O2- produced by the autoxidation of respiratory chain electron carriers, and other cellular reductants, inactivates bacterial and mammalian iron-sulfur-containing (de)hydratases including the citric acid cycle enzyme aconitase. Release of the solvent-exposed iron atom and oxidation of the [4Fe-4S]2+ cluster accompanies loss of catalytic activity. Rapid reactivation is achieved by iron-sulfur cluster reduction and Fe2+ insertion. Inactivation-reactivation is a dynamic and cyclical process which modulates aconitase and (de)hydratase activities in Escherichia coli and mammalian cells. The balance of inactive and active aconitase provides a sensitive measure of the changes in steady-state O2- levels occurring in living cells and mitochondria under stress conditions. Aconitases are also inactivated by other oxidants including O2, H2O2, NO, and ONOO- which are associated with inflammation, hyperoxia and other pathophysiological conditions. Loss of aconitase activity during oxidant stress may impair energy production, and the liberation of reactive iron may further enhance oxidative damage. Iron-sulfur center cycling may also serve adaptive functions by modulating gene expression or by signaling metabolic quiescence.
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PMID:Superoxide-driven aconitase FE-S center cycling. 917 19

Oxidative insults that are lethal to epithelial cells kill either via apoptosis or necrosis. Nuclear factor-kappaB (NF-kappaB) is a redox-sensitive transcription factor that is activated by oxidative insult, and NF-kappaB activation can protect cells from apoptosis. To test if NF-kappaB can protect from necrotic cell death caused by high levels of molecular O2 (hyperoxia), we exposed human alveolar epithelial (A549) cells to hyperoxia. NF-kappaB was shown to be activated and was translocated to the nucleus within minutes. Nuclear translocation persisted over the course of several days, and the levels of NF-kappaB protein and mRNA increased as well. In hyperoxia, NF-kappaB regulation was independent of mitogen-activated protein kinase (MAPK). In sharp contrast, there was neither nuclear translocation of NF-kappaB nor any increase in expression after exposure to H2O2 at a concentration where this oxidant induces both MAPK and widespread apoptosis. Despite the activation and increased expression of NF-kappaB in hyperoxia, this oxidant remained lethal to the cells. These observations confirm the notion that apoptosis occurs in the absence of NF-kappaB activation but indicate that protection from cell death by NF-kappaB is probably limited to apoptosis.
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PMID:Nuclear factor-kappaB is activated by hyperoxia but does not protect from cell death. 925 81

Reactive oxygen species (ROS) are involved in a number of disease states where they are believed to be responsible for cellular damage. In this study we examined the effect of ROS generation on polyamine catabolism. Treatment of human breast cancer cells with either H2O2 or hyperoxia increased the activity of spermidine/spermine N1-acetyltransferase (SSAT). These increases occurred before any significant signs of cellular injury. Agents known to decrease the production of reactive oxygen species such as dimethylthiourea and o-phenanthroline prevented the increase in SSAT activity indicating ROS involvement in the induction process. These results suggest that induction of SSAT may be a protective response to oxidative stress in mammalian cells facilitating removal of polyamines from the cell to prevent their toxic accumulation.
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PMID:Induction of spermidine/spermine N1-acetyltransferase in human cancer cells in response to increased production of reactive oxygen species. 960 36

Bronchial epithelial cells are the first cells to encounter high concentrations of inspired oxygen, and their damage is a typical feature in many airway diseases. The direct effect of oxygen on the expression of the main antioxidant enzymes (AOEs) in human bronchial epithelial cells is unknown. We investigated the messenger RNA (mRNA) levels of manganese superoxide dismutase (MnSOD), copper-zinc superoxide dismutase (CuZnSOD), catalase (CAT), and glutathione peroxidase (GPx), as well as the specific activities of MnSOD, CuZnSOD, CAT, GPx, and glutathione reductase, in BEAS-2B bronchial epithelial cells exposed to hyperoxia (95% O2, 5% CO2) for 16 to 48 h. We also assessed the resistance of cells preexposed to hyperoxia to subsequent oxidant stress. Significant cell injury was observed after 72 h exposure to hyperoxia; release of lactate dehydrogenase (LDH) from control cells and cells exposed to hyperoxia for 72 h was 7.0 +/- 1.0% and 22.0 +/- 1.0%, respectively. Hyperoxia for 16 h, 24 h, or 48 h had no effect on the mRNA levels or specific activities of any of these enzymes. Despite their unchanged AOE levels, cells exposed to hyperoxia for 48 h showed increased resistance to H2O2 and menadione. Total glutathione content of the cells increased by 55% and 58% after 24 h and 48 h, respectively, compared with normoxic controls. However, glutathione depletion with buthionine sulfoximine (BSO) did not diminish the oxidant resistance of hyperoxia-exposed cells. We conclude that AOEs in human bronchial epithelial cells are not directly upregulated by high oxygen tension, and that increases in AOE-specific activities or glutathione are not necessary for the development of increased oxidant resistance in these cells.
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PMID:Antioxidant enzyme regulation and resistance to oxidants of human bronchial epithelial cells cultured under hyperoxic conditions. 969 1

The gene expression of heme oxygenase-1 (HO-1) was studied in mammalian cell lines exposed to hyperoxia. Northern blot analysis demonstrated that hyperoxic exposure increased the HO-1 mRNA levels in various types of cells, including human hepatoma (HepG2) cells. This increase was time- and dose-dependent, and reversible. The HO-1 mRNA levels in HepG2 cells were increased to 2.3- and 4.2-fold of the control by hyperoxic exposure of 6 and 23 h, respectively. Cycloheximide and actinomycin D inhibited the increases in the HO-1 mRNA level produced by hyperoxia, indicating that response to hyperoxia is dependent on de novo protein synthesis and mRNA transcription. Antioxidants, desferrioxamine (DES) and o-phenanthroline (OP) partially inhibited the HO-1 mRNA elevation by hyperoxia. In addition to hyperoxia, sodium arsenite (NaAsO2), cadmium chloride (CdCl(2)) and hydrogen peroxide (H2O2), which are reactive oxygen intermediates (ROI) generators, increased the HO-1 mRNA level by 11-, 22- and 2.5-fold, respectively. OP, an antioxidant and a bivalent metal chelator, blocked the HO-1 mRNA elevation induced either by hyperoxia or by the three ROI generators. In contrast to OP, N-acetylcysteine (NAC), an antioxidant and membrane-permeable reducing reagent, enhanced the HO-1 mRNA elevation induced by hyperoxia, although NAC inhibited the mRNA elevation induced by NaAsO2, CdCl2 and H2O2. These results indicate that oxygen tension regulates HO-1 gene expression and suggest that hyperoxia-specific and redox-sensitive regulators may be involved in hyperoxia-mediated HO-1 gene expression.
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PMID:Oxygen tension regulates heme oxygenase-1 gene expression in mammalian cell lines. 974 10

The aims of this study were to investigate the effect of hyperoxia on O2(-.), H2O2 and .NO generation and iNOS mRNA levels in rat type II pneumocytes in vitro and the possible protective effect of the lazaroid U-74389G. Rat type II pneumocytes were exposed, 36 h after isolation, to air, 60% or 85% O2 for 48 h. At the beginning of the experiment and 24 h later, the cells were exposed for 30 min to either 30 microM U-74389G or only the vehicle for the lazaroid (control). Exposure to 60% and 85% O2 decreased nitrite production 2.9-fold and 3.9-fold, and increased O2(-.) and H2O2 generation 4.6-fold and 6.7-fold, respectively. In the 85% O2-exposed cells, hyperoxia increased lipid peroxidation (thiobarbituric acid reactive substances, TBARS production) 2-fold and iNOS mRNA production 5.4-fold. U-74389G prevented the decrease in nitrite and the rise in O2(-.) and H2O2 production, the increase in TBARS and the rise in iNOS mRNA after hyperoxia. We conclude that exposure of type II pneumocytes in vitro to subtoxic oxygen levels leads to a disturbance in the .NO-O2(-.) balance despite increased iNOS mRNA levels. The lazaroid U-74389G appears to be a useful compound in the protection of hyperoxic lung injury by restoration of this .NO-O2(-.) balance and prevention of TBARS formation.
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PMID:Protective effects of the lazaroid U-74389G against hyperoxia in rat type II pneumocytes. 980 60


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