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

Factors responsible for the loss of respiratory burst capacity (stimulated extracellular O2-. release) of alveolar macrophages (AM) exposed to prolonged hyperoxia were assessed. Specific pathogen-free rats were exposed to 1 ATA O2 for 24-72 h, and lungs of survivors lavaged. Release of O2-. by cells after addition of concanavalin A, which stimulated AM but not polymorphonuclear leukocytes (PMN), or digitonin, which stimulated both cell types, was measured using cytochrome c reduction +/- superoxide dismutase. O2-. release by AM declined 47.2% (P less than 0.05) after 24 h of hyperoxia and 100% after 60 h. Percent PMN in the lavage was less than 3% at 0-36 h but increased to 16% at 48 h and to 44% at 72 h. Although addition of PMN to AM in vitro caused inhibition of AM O2-. release, the percent PMN required for inhibition was not reached in vivo until after a significant decline in AM O2-.-releasing capacity had already occurred. Cell-free lavage fluid from either control or hyperoxic rats did not affect AM O2-. release. AM in culture for 24 h in hyperoxia lost 76.7% (P less than 0.005) of O2-.-releasing capacity vs. cells incubated in 20% O2, although dye exclusion was unaffected. The results indicate that the major cause of loss of AM O2-. release by hyperoxia is a direct effect of O2 on the cells.
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PMID:Hyperoxia inhibits stimulated superoxide release by rat alveolar macrophages. 629 Apr 36

This study examined the effects of hyperoxic training on specific cardiorespiratory and metabolic responses. A group of 19 male subjects trained for 5 weeks on a cycle ergometer at 70 percent of hyperoxic or normoxic maximal heart rate, the hyperoxic group (HG) breathing 70 percent O2, the normoxic group (NG) breathing 21 percent O2. The subjects were tested pre- and post-training under both hyperoxia and normoxia. Measurements included cardiac output (Q(c)), stroke volume (SV), heart rate (HR), pulmonary ventilation (V(E)), oxygen consumption (VO(2)), partial pressure of oxygen (PO(2)), partial pressure of inspired carbon dioxide (PCO(2)), blood lactate concentration [La], and fiber type composition. The V(E) was significantly lower at submaximal work rates (P <0.05) and maximal V(E) increased after training in both groups for both test conditions; hyperoxic V(E) was lower than normoxic V(E) (P <0.05). The maximal V0(2) increased significantly (P <0.05) in both groups for both tests and was 11 percent - 12 percent higher during hyperoxia. Post-training maximal heart rate (HR(max)) was significantly decreased (P <0.05) at the same absolute work rate regardless of the training group or test type. The SV was increased at each work rate and Q c was unchanged. The maximal Q(c) increased significantly (P <0.05) for both groups and types of test: for normoxia: NG 27.3-30.41*min(-1) and HG 30.3-32.31*min(-1) and for hyperoxia: NG 24.7-25.6 and HG 27.9-31.21*min(-1). Although working at the same intensity relative to HR(max), HG showed significantly lower [La] following a single training session, yet maximal values were unchanged after training. Both groups showed a significant increase in the percentage of type IIA fibers post-training but HG retained a larger percentage of IIB fibers. Mitochondrial enzymes; citrate kinase, 3-hydroxyacyl CoA dehydrogenase, and cytochrome c-oxidase were increased in the normoxic trained subjects (P <0.05). In summary, training induced adaptive responses in maximal aerobic power, HR, SV, Q(c), [La], and muscle fiber type composition, independent of inspired PO(2). Intramuscular data suggested there may be some differences between hyperoxic and normoxic training and these were substantiated by mitochondrial enzyme and lactate findings. Our data would suggest that transport mechanisms may limit the ability to increase aerobic power.
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PMID:Cardiorespiratory and metabolic adaptations to hyperoxic training. 886 67

Cytochrome c is a component of the mitochondrial electron transport chain, where it transfers electrons from ubiquinol-cytochrome c reductase to cytochrome c oxidase. Autoxidation of some of the components of the electron transport chain is the main source of intracellular O(2)(-*)/H(2)O(2) production in aerobic organisms. Because cytochrome c is located on the outer surface of the inner mitochondrial membrane, it is likely to be constantly exposed to H(2)O(2), secreted by mitochondria into the cytosol. The specific objective of this study was to determine whether cytochrome c in the flight muscle mitochondria of the housefly is oxidatively damaged during aging and/or under severe oxidative stress induced by exposure of flies to 100% oxygen. Results of two independent methods, namely tritiated borohydride labeling for determining carbonylation and mass spectral analysis for the measurement of molecular mass, indicated that neither the carbonyl level nor the molecular mass of cytochrome c was affected by aging or hyperoxia. Thus, either cytochrome c is resistant to oxidative damage in vivo or the oxidized cytochrome c is promptly degraded. These findings also support the concept that protein oxidative damage during aging and under oxidative stress is selective.
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PMID:Effects of aging and hyperoxia on oxidative damage to cytochrome c in the housefly, Musca domestica. 1096 9

Cytochrome oxidase activity from the retina can be enhanced or depressed by free radical-mediated reactions both in positive and negative aspect. The greatest effect was exerted by ischemia/reperfusion, which significantly increased the fluorescent products of lipid peroxidation (358 %, P < 0.01) and inhibited the enzyme activity (14%, P < 0.001). After hyperoxia the fluorescent products slightly increased (192%, P < 0.05) as well as the enzyme activity (133 %, P < 0.05). Hypoxia had no effect on any of these parameters. Specific changes in the composition of fluorophores after ischemia/reperfusion were revealed in the fluorescence spectra. The fact that increased lipid peroxidation after hyperoxia and after ischemia/reperfusion does not produce the same effect upon cytochrome oxidase activity might be explained by changes in the kinetic behavior of cytochrome oxidase. In the control enzyme preparation, two binding sites for cytochrome c were observed. One was of the low-affinity (Km = 60 microM) and the other of the high-affinity (Km = 1.12 microM). After in vitro-initiated lipid peroxidation, the low-affinity binding site was lost and the activity measured under "optimum" conditions at a single cytochrome concentration was higher than in the controls. This implies that oxidative damage to cytochrome oxidase in vivo can be site-specific and its extent should be estimated by performing detailed kinetic analysis as otherwise the results might be misleading.
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PMID:The effects of hyperoxia, hypoxia, and ischemia/reperfusion on the activity of cytochrome oxidase from the rat retina. 1152 37

Exposure of animals to hyperoxia results in lung injury that is characterized by apoptosis and necrosis of the alveolar epithelium and endothelium. The mechanism by which hyperoxia results in cell death, however, remains unclear. We sought to test the hypothesis that exposure to hyperoxia causes mitochondria-dependent apoptosis that requires the generation of reactive oxygen species from mitochondrial electron transport. Rat1a cells exposed to hyperoxia underwent apoptosis characterized by the release of cytochrome c, activation of caspase-9, and nuclear fragmentation that was prevented by the overexpression of Bcl-X(L.) Murine embryonic fibroblasts from bax(-/-) bak(-/-) mice were resistant to hyperoxia-induced cell death. The administration of the antioxidants manganese (III) tetrakis (4-benzoic acid) porphyrin, ebselen, and N-acetylcysteine failed to prevent cell death following exposure to hyperoxia. Human fibrosarcoma cells (HT1080) lacking mitochondrial DNA (rho(0) cells) that failed to generate reactive oxygen species during exposure to hyperoxia were not protected against cell death following exposure to hyperoxia. We conclude that exposure to hyperoxia results in apoptosis that requires Bax or Bak and can be prevented by the overexpression of Bcl-X(L). The mitochondrial generation of reactive oxygen species is not required for cell death following exposure to hyperoxia.
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PMID:Hyperoxia-induced apoptosis does not require mitochondrial reactive oxygen species and is regulated by Bcl-2 proteins. 1187 88

Pre-term neonates and neonates in general exhibit physiological vitamin E deficiency and are at increased risk for the development of acute lung diseases. Apoptosis is a major cause of acute lung damage in alveolar type II cells. In this paper, we evaluated the hypothesis that vitamin E deficiency predisposes alveolar type II cells to apoptosis. Therefore, we measured markers of apoptosis in alveolar type II cells isolated from control rats, vitamin E deficient rats and deficient rats that were re-fed a vitamin E-enriched diet. Bax and cytosolic cytochrome c increased, and the mitochondrial transmembrane potential and Hsp25 expression was reduced in vitamin E deficiency. Furthermore, increased DNA-fragmentation and numbers of early and late apoptotic cells were seen, but caspases 3 and 8 activities and expression of Fas, Bcl-2, Bcl-x and p53 remained unchanged. Vitamin E depletion did not change the GSH/GSSG ratio and the activities of antioxidant enzymes. Thus, vitamin E deficiency may induce a reversible pro-apoptotic response in lung cells and sensitise them for additional insult. In agreement with this hypothesis, we demonstrate that in vivo hyperoxia alone does not induce apoptosis in type II cells of control rats but reversibly increases DNA-fragmentation and numbers of early apoptotic type II cells in vitamin E-depleted cells.
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PMID:Vitamin E deficiency sensitizes alveolar type II cells for apoptosis. 1206 53

Therapy with high oxygen concentrations (hyperoxia) is often necessary to treat patients with respiratory failure. However, hyperoxia may exacerbate the development of acute lung injury, perhaps by increasing lung epithelial cell death. Therefore, interrupting lung epithelial cell death is an important protective and therapeutic strategy. In the present study, hyperoxia (95% O(2)) results in murine lung epithelium cell death by DNA-laddering, terminal deoxynucleotidyltransferase dUTP nick end labeling, and Annexin V-fluorescein isothiocyanate flow cytometry assay. We show that hyperoxia increases superoxide production, as assessed by nicotinamide adenine dinucleotide phosphate reduced (NADPH) oxidase activity and flow cytometric assay, and increases phospho-extracellular signal-regulated kinase (ERK)1/2 by Western blot analysis. These processes are inhibited by a reactive oxygen species inhibitor, diphenylene iodonium (DPI), and by an inhibitor of the mitogen-activated protein (MAP) or ERK kinase (MEK)/ERK1/2 pathway, PD98059. ERK1/2 activation in hyperoxia is also inhibited by DPI. Hyperoxia-induced cell death is associated with cytochrome c release, subsequent caspase 9 and 3 activation, and poly (ADP-ribosyl) polymerase cleavage, which can all be suppressed by DPI and PD98059. However, the broad caspase inhibitor z-VAD-FMK protects cells from death without affecting superoxide generation and ERK1/2 activation. Taken together, our data suggest that hyperoxia, by virtue of activating NADPH oxidase, generates reactive oxygen species (ROS), which mediates cell death of lung epithelium via ERK1/2 MAPK activation, and functions upstream of caspase activation in lung epithelial cells.
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PMID:Reactive oxygen species and extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase mediate hyperoxia-induced cell death in lung epithelium. 1259 56

Hyperoxia is known to induce extensive alveolar cell death by still poorly defined mechanisms. In this study, the mitochondria-dependent cell death pathway was explored during hyperoxia-induced lung injury in mice. We observed a progressive release of cytochrome c from the mitochondria into the cytosol of alveolar cells. This release was accompanied by the translocation of the proapoptotic protein Bax from cytosol to mitochondria without detectable activation of caspase-3. As cytochrome c release can be induced by mitochondrial membrane alteration and permeability transition (MPT), mice were treated with cyclosporin A, which specifically inhibits MPT. Cyclosporin A treatment prevented mitochondrial release of cytochrome c during hyperoxia and concomitantly preserved mitochondria from extensive swelling and crista disorganization, as assessed by electron microscopy analysis of alveolar epithelial cells. These morphological and biochemical observations correlated with decreased lung tissue damage, as evaluated by morphological score and lung weight. In conclusion, mitochondrial damage and cytochrome c release are important linked events in hyperoxia-induced lung injury and can be efficiently blocked by cyclosporin A.
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PMID:Mitochondrial cytochrome c release is a key event in hyperoxia-induced lung injury: protection by cyclosporin A. 1452 30

Hypoxic brain injury during fetal or neonatal development leads to damaged immature neurons and can result in cognitive or behavioral dysfunction. Hyperoxia therapy (treatment with oxygen) is commonly applied to infants with signs of perinatal hypoxia-anoxia. Both hypoxia and hyperoxia have been shown to result in apoptosis in the brains of rats in several animal models. One determinant of cellular commitment to cell death is the differential expression of the Bcl-2 family of proteins in response to trauma. Here, we characterize cell death and the expression of Bcl-2 homologous proteins in 7-day-old neonatal rat cerebral cortex after hypoxia (5% O(2) for 40 min) and/or hyperoxia (>95% O(2) for 2 h after hypoxia). The expression of Bcl-2 and Bcl-X(L), two anti-apoptotic proteins, decreased at 24 h after hypoxia. Bcl-X(L) increased after either hyperoxia or hypoxia+hyperoxia. We did not detect significant changes in the cytoplasmic levels of pro-apoptotic protein Bax after any of these three treatments. Using cell death ELISA and DNA FragEL assays, we observed increased cell death at 24h after hypoxia, hyperoxia or hypoxia+hyperoxia treatments. At 24 h after either hypoxia, hyperoxia or hypoxia+hyperoxia, caspase 3 activity also increased significantly. Our results suggest that both hypoxia and hyperoxia alone can induce cell death. The Bcl-2 --> cytochrome c --> caspase 3 pathway played a role in hypoxia-induced cell death, while other pathways may be involved in hyperoxia-induced cell death.
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PMID:Bcl-2 family members make different contributions to cell death in hypoxia and/or hyperoxia in rat cerebral cortex. 1459 83

Exposure of animals to hyperoxia results in respiratory failure and death within 72 h. Histologic evaluation of the lungs of these animals demonstrates epithelial apoptosis and necrosis. Although the generation of reactive oxygen species (ROS) is widely thought to be responsible for the cell death observed following exposure to hyperoxia, it is not clear whether they act upstream of activation of the cell death pathway or whether they are generated as a result of mitochondrial membrane permeabilization and caspase activation. We hypothesized that the generation of ROS was required for hyperoxia-induced cell death upstream of Bax activation. In primary rat alveolar epithelial cells, we found that exposure to hyperoxia resulted in the generation of ROS that was completely prevented by the administration of the combined superoxide dismutase/catalase mimetic EUK-134 (Eukarion, Inc., Bedford, MA). Exposure to hyperoxia resulted in the activation of Bax at the mitochondrial membrane, cytochrome c release, and cell death. The administration of EUK-134 prevented Bax activation, cytochrome c release, and cell death. In a mouse lung epithelial cell line (MLE-12), the overexpression of Bcl-XL protected cells against hyperoxia by preventing the activation of Bax at the mitochondrial membrane. We conclude that exposure to hyperoxia results in Bax activation at the mitochondrial membrane and subsequent cytochrome c release. Bax activation at the mitochondrial membrane requires the generation of ROS and can be prevented by the overexpression of Bcl-XL.
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PMID:Reactive oxygen species are required for hyperoxia-induced Bax activation and cell death in alveolar epithelial cells. 1462 74


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