UMLS:C0242706 - FACTA Search

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

Nitroxide stable free radicals have previously been found to afford protection in various biological systems against diverse types of oxidative stress, including, ischemia/reperfusion, hyperoxia, mechanical trauma, toxic xenobiotics, ionizing radiation, gastric and colonic irritants or strong oxidants. Dismutation of superoxide has originally been suggested to be one of the mechanisms that underlie the anti-oxidant effect of nitroxides. However, no direct evidence has been found, so far, to support this assumption. In the present study, superoxide and H2O2, generated enzymatically, were used to directly inactivate papain, a sulfhydryl enzyme, in vitro. The rate of papain inactivation served to assess the damage. The reaction mixtures contained a chelate in order to prevent the effect of adventitious redox-active metal ions, pre-empt the Fenton reaction and avoid hydroxyl-induced damage. Catalase or SOD alone partially protected the papain from inactivation. The protective effect of nitroxides resembled that of SOD in several aspects: a) nitroxides provided partial protection; b) the protective effect of nitroxides did not increase with the elevation of their concentration (above 0.5 mM); c) the combined addition of SOD and the nitroxide did not provide greater protection than that demonstrated by nitroxides or SOD separately; d) the effects of catalase with the nitroxide were additive; e) the nitroxide, like SOD itself, did not protect papain from H2O2-induced inactivation; f) the nitroxide was found not to be consumed in the course of the reaction but rather to be recycled. The results indicate that: (a) the main species responsible for the papain inactivation in a system in which the effect of transition metals is pre-empted, are O2-. and H2O2; (b) nitroxides inhibit the oxidative damage by removing superoxide not stoichiometrically, but rather catalytically as SOD-mimics; (c) nitroxides do not afford protection when the oxidative damage is induced directly by H2O2 (and not mediated by redox-active metals).
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PMID:An SOD-mimicry mechanism underlies the role of nitroxides in protecting papain from oxidative inactivation. 982 49

Leukocyte infiltration plays a major role in ischemia-associated organ dysfunction and damage. A crucial step for extravasation of white blood cells is binding of leukocyte beta-integrins to endothelial adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1). To test for direct effects of oxygen on this process we studied ICAM-1 and VCAM-1 expression in human dermal microvascular and umbilical vein endothelial cells (EC) exposed to different oxygen tensions in the absence or presence of tumor necrosis factor-alpha (TNF-alpha). Hypoxia (95% N2-5% CO2) resulted in a downregulation of basal but not TNF-alpha-induced expression of ICAM-1 and VCAM-1. Subsequent rises in oxygen (21, 40, or 95% O2) led to marked increase of ICAM-1 and VCAM-1 cell surface and mRNA expression in both EC types, which after 16 h amounted to about one-third to one-half of maximal TNF-alpha-induced expression. This increase was greatest after 0.5-h hypoxia and was blunted with prolonged hypoxic preincubation. Exposure of cells preincubated under "normoxic" (21% O2) conditions to hyperoxia (40 or 95% O2) also enhanced expression of both adhesion molecules, but the increase was lower than in cells preexposed to hypoxia. The nitric oxide synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) enhanced ICAM-1 and VCAM-1 expression under basal and hypoxic conditions, but in the presence of L-NAME, levels in reoxygenated cells were not higher than basal levels. Moreover, the oxygen-induced rise could be mimicked by addition of H2O2 to normoxic cells, and the oxygen-induced expression of VCAM-1 but not of ICAM-1 was inhibited by addition of the free radical scavengers superoxide dismutase, N-acetyl-L-cysteine, and pyrrolidinedithiocarbamate. These data indicate that an increase in oxygen availability stimulates ICAM-1 and VCAM-1 expression on micro- and macrovascular EC, which may contribute to adhesion and transmigration of different leukocyte populations in ischemia-reperfusion injuries.
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PMID:Increases in oxygen tension stimulate expression of ICAM-1 and VCAM-1 on human endothelial cells. 1036 86

To test whether exogenous oxidants alter intracellular oxidant levels in skeletal muscle fibres, we exposed rat diaphragm to donors of nitric oxide (NOx), reactive oxygen species (ROS) or hyperoxia, and monitored intracellular oxidant levels using a fluorescent probe. Fibre bundles were dissected from the diaphragm and loaded with 2', 7'-dichlorodihydrofluorescein (DCFH); emissions were monitored using a fluorescence microscope. DCFH-loaded muscles were exposed to either a NOx donor (1 mM S-nitroso-N-acetyl penicillamine, SNAP; 1 mM sodium nitroprusside, SNP; 400 microM 1-hydroxy-2-oxo-3-(N-3-methyl-aminopropyl)-3-methyl-1-triazen, NOC-7), an ROS donor (100 microM hydrogen peroxide, H2O2; 100 microM tert-butyl hydroperoxide; 1 mM hypoxanthine plus 0.01 U mL-1 xanthine oxidase, HXXO) or a range of PO2s (25, 60 or 95% O2 oxygenating Krebs-Ringer solution) for 40 min; time-matched control bundles remained in Krebs-Ringer solution. Control muscles oxidized DCFH at a rate of 0.32 +/- 0.1 greyscale units min-1. SNAP (766%), SNP (1244%), NOC-7 (851%), H2O2 (543%), and HXXO (541%) increased DCFH oxidation from control levels. The increase in emissions caused by NOC-7 and SNP were blunted by the NOx scavenger haemoglobin (1 microM). DCFH oxidation by HXXO was unaffected by 1000 U mL-1 superoxide dismutase but was significantly decreased by 1000 U mL-1 catalase and 1 mM salicylate. PO2 had no effect on intracellular oxidant levels. Therefore, extracellular NOx and ROS can alter intracellular oxidant status in skeletal muscle fibres. These observations suggest that intrafibre oxidant levels could be the result of both intracellular and extracellular oxidant production.
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PMID:Exogenous reactive oxygen and nitric oxide alter intracellular oxidant status of skeletal muscle fibres. 1038 90

Vascular endothelial cell apoptosis has previously been shown to play a role in the pathogenesis of hypertension-induced vessel deletion and damage. In the present in vitro study we analyse several possible relevant causative factors of vascular endothelial cell apoptosis, namely, serum deprivation and nutrient depletion, oxidative stress in the forms of hypoxia, hyperoxia or free radical damage, and altered levels of transforming growth factor-beta1 (TGF-beta1) protein. An established cell line, bovine aortic endothelial cells (BAEC), was maintained in complete growth medium (RPMI-1640 plus 15% fetal calf serum and antibiotics, abbreviated as RPMI) in 25cm2 flasks or in 12-well plates on glass coverslips. Confluent but actively-growing cultures were treated with either hypoxia (PO2 of RPMI = 50mmHg), serum-free media (SFM), SFM plus hypoxia, hyperoxia (PO2 of RPMI = 450mmHg), hydrogen peroxide (H2O2, 1mM) in SFM, or TGF-beta1 protein (10ng/mL) in SFM. Appropriate control cultures were used. BAEC were collected 48h or 72h after all treatments except for TGF-beta1 and H2O2 treatments that were collected at 16-18h. Cell death was assessed using morphological characteristics or in situ end labeling (ISEL), cell proliferation assessed using proliferating cell nuclear antigen (PCNA), and TGF-beta1 expression assessed using transcript levels or immunohistochemistry. All treatments significantly increased levels of apoptosis over control cultures (P<0.05), and decreased levels of cell proliferation. Treatment with TGF-beta1 protein or SFM plus hypoxia induced greatest levels of apoptosis. TGF-beta1 protein and transcript levels were decreased in treated cultures, results suggesting that a paracrine source of TGF-beta1 protein would be needed as a cause of endothelial cell apoptosis in viva. Future therapies against inappropriate vessel deletion in disease states may use the known gene-driven nature of apoptosis to modify this sort of cell death in endothelial cells.
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PMID:Apoptosis in vascular endothelial cells caused by serum deprivation, oxidative stress and transforming growth factor-beta. 1059 59

Nitric oxide (NO) shows cytotoxicity, and its reaction products with reactive oxygen species, such as peroxynitrite, are potentially more toxic. To examine the role of O2 in the NO toxicity, we have examined the proliferation of cultured human umbilical vein endothelial cells in the presence or absence of NO donor, ((Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-++ +ium-1,2-diolate) (DETA-NONOate) (100-500 microM), under normoxia (air), hypoxia (< 0.04% O2) or hyperoxia (88-94% O2). It was found that the dose dependency on NONOate was little affected by the ambient O2 concentration, showing no apparent synergism between the two treatments. We have also examined the effects of exogenous NO under normoxia and hyperoxia on the cellular activities of antioxidant enzymes involved in the H2O2 elimination, since many of them are known to be inhibited by NO or peroxynitrite in vitro. Under normoxia DETA-NONOate (500 microM) caused 25% decrease in catalase activity and 30% increases in glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities in 24h. Under hyperoxia NO caused about 25% decreases in activities of catalase, glutathione reductase and glucose-6-phosphate dehydrogenase. The H2O2 removal rate by NO-treated cells was computed on the mathematical model for the enzyme system. It was concluded that the cellular antioxidant function is little affected by NO under normoxia but that it is partially impaired when the cells are exposed to NO under hyperoxia.
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PMID:Interactions of nitric oxide and oxygen in cytotoxicity: proliferation and antioxidant enzyme activities of endothelial cells in culture. 1088 22

The airway epithelium is injured by oxidants inhaled as atmospheric pollutants or produced during inflammatory responses. We studied the effect of modulating the antioxidant intracellular glutathione, both using thiol compounds and by the adaptive effect of hyperoxia, on oxidant-induced injury and activation of the nuclear factor-kappaB (NF-kappaB) in two cell lines: the human bronchial (16HBE) and type II alveolar epithelial cells (A549). The thiol antioxidants glutathione (GSH) and glutathione monoethyl ester (GSH-MEE) [2 mM] increased GSH levels (nmol/mg protein) in A549 cells (GSH 383 +/- 26 and GSH-MEE 336 +/- 23 vs control 171 +/- 13, P < 0.001) and in 16HBE cells (GSH 405 +/- 33, GSH-MEE 362 +/- 37 vs control 198 +/- 12, P < 0.001, N = 3). Treatment of hyperoxia (95% oxygen) also increased GSH levels between 4 and 24 hr exposure compared with control (P < 0.01). Hydrogen peroxide (H(2)O(2)) (0.01 mM) induced NF-kappaB activation, whereas hyperoxia exposure did not affect NF-kappaB activation in either cell line. Pretreatment with dl-buthionine (SR)-sulfoximine, which decreased intracellular glutathione, increased NF-kappaB binding induced by H(2)O(2) and increased lactate dehydrogenase (LDH) release (P < 0.001). Pretreatment with the thiol compounds and hyperoxia totally inhibited H(2)O(2)-induced NF-kappaB binding and cell injury as measured by LDH release. These data indicate the importance of intracellular glutathione and inhibition of NF-kappaB in both protection/tolerance against oxidant-induced epithelial cell injury, and NF-kappaB activation in response to oxidative stress which may be important in lung inflammation. Thus, increasing intracellular glutathione may be of therapeutic relevance if able to modulate NF-kappaB activation and hence attenuate inflammation.
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PMID:Oxidant-mediated lung epithelial cell tolerance: the role of intracellular glutathione and nuclear factor-kappaB. 1155 25

Xanthine oxidoreductase (XOR) catalyzes the final reactions of purine catabolism and may account for cell damage by producing reactive oxygen metabolites in cells reoxygenated after hypoxia. We found a three- to eightfold higher XOR activity in cultured human bronchial epithelial cells exposed to hypoxia (0.5-3% O2) compared with cells grown in normoxia (21% O2) but no difference in XOR protein or mRNA. XOR promoter constructs failed to respond to hypoxia. The cellular XOR activity at 3% O2 returned to basal levels when the cells were returned to 21% O2, and hyperoxia (95% O2) abolished enzyme activity with no change in XOR protein. Our data suggest reversible enzyme inactivation by oxygen or its metabolites. NADH was normally oxidized by the oxygen-inactivated enzyme, which rules out damage to the flavin adenine dinucleotide cofactor. Hydrogen peroxide partially inactivated the molybdenum center of XOR, as shown by a parallel decrease in XOR-catalyzed xanthine oxidation and dichlorophenolindophenol reduction. We conclude that the transcription or translation of XOR is not influenced by hypoxia or hyperoxia. Instead, the molybdenum center of XOR is posttranslationally inactivated by oxygen metabolites in "normal" (21% O2) cell culture atmosphere. This inactivation is reversed in hypoxia and accounts for the apparent induction.
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PMID:Posttranslational inactivation of human xanthine oxidoreductase by oxygen under standard cell culture conditions. 1263 68

Acute lung injury is a frequent and treatment-limiting consequence of therapy with 100% oxygen. Previous studies have determined that both interleukin (IL)-6 and IL-11 are protective in oxygen toxicity. This protection was associated with markedly diminished alveolar-capillary protein leak, endothelial and epithelial membrane injury, lipid peroxidation, and pulmonary neutrophil recruitment. Hyperoxia also caused cell death with DNA fragmentation in the lungs of transgene (-) animals, and both IL-6 and IL-11 markedly diminished this cell death response. However, the mechanism(s) by which these cytokines protect cells from death is unclear. In the present study, we characterized the effects of H2O2 on subconfluent human umbilical vein endothelial cell (HUVEC) and human pulmonary microvascular endothelial cell (HPMEC) cultures. We found that preincubation of HUVEC cultures with either IL-6 or IL-11 diminished H2O2 (1.0 mM)-induced cell death. Similar effects were noted with HPMEC showing that this effect is not HUVEC-specific. The protective effects of both IL-6 and IL-11 were not associated with any changes in antioxidants and were decreased by approximately 80% in the presence of U0126, a specific inhibitor of MEK-1-dependent pathways. The cytoprotective effects of IL-11 and IL-6 were also completely eliminated in STAT3 dominant-negative transduced HUVEC cultures. These studies demonstrate that IL-6 and IL-11 both confer cytoprotective effects that diminish oxidant-mediated endothelial cell injury. They also demonstrate that this protection is mediated, at least in part, by a STAT3 and MEK-1-dependent specific signal transduction pathway(s).
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PMID:Interleukin-11 and interleukin-6 protect cultured human endothelial cells from H2O2-induced cell death. 1273 73

Oxidant insults can lead to apoptotic and nonapoptotic cell death. Lung epithelial cells exposed to high levels of oxygen do not die via apoptosis, but through a much slower, morphologically distinct process involving cell and nuclear swelling. In contrast, H2O2 induces a rapid apoptotic cell death. We first assessed the effect of oxidant exposure on activator protein-1 (c-Jun and Fos) and c-Jun N-terminal kinase (JNK) regulation in MLE12 cells. Both oxidants induced c-Jun and Fos expression, albeit with a different pattern of regulation-hyperoxia (95% O2) induced a biphasic response, whereas H2O2 (500 microM) induced a sustained response. We then examined the role of JNK by Western blot, JNK activity assay, and a pull-down assay and observed an identical pattern of regulation. To assess whether JNK functions in a pro-death or pro-survival capacity, we generated stable cell lines that constitutively express a dominant-negative mutation of JNK resulting in significant inhibition of JNK activity. Inhibition of the JNK pathway in this manner prevented hyperoxic and H2O2-induced cell death. These results demonstrate that hyperoxic cell death is pathway-driven and that both modes of death involve the JNK signaling pathway.
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PMID:Inhibition of c-Jun N-terminal kinase pathway improves cell viability in response to oxidant injury. 1284 52

1-Cys peroxiredoxin (1-cysPrx), a member of the peroxiredoxin family that contains a single conserved cysteine residue, reduces a broad spectrum of hydroperoxides. We studied changes in 1-cysPrx expression in rat lungs and lung cell lines in response to oxidative stress due to hyperoxia, H2O2, or paraquat. After 60 h of hyperoxia (>95% O2), mRNA and protein levels of 1-cysPrx and peroxidase activity were significantly elevated in rat lungs by approximately 1.5- to 2-fold compared with the control (P < 0.05). A similar induction of 1-cysPrx was observed in mouse lungs following exposure to O2 for 63 or 72 h; enzyme induction in mouse lungs was similar for wild-type and glutathione peroxidase 1 gene-targeted mice. H2O2 and paraquat treatment induced 1-cysPrx gene expression in L2 cells. Enzyme induction was attenuated by pretreatment with Trolox or N-acetylcysteine. Actinomycin D treatment showed that stability of 1-cysPrx mRNA was not altered in the presence of H2O2 or paraquat, indicating that increased expression with oxidative stress is regulated at the transcriptional level. These data indicate that the antioxidant enzyme 1-cysPrx is induced in lung cells by oxidative stress.
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PMID:Induction of 1-cys peroxiredoxin expression by oxidative stress in lung epithelial cells. 1285 Dec 11

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