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

Pulmonary neuroendocrine cell (PNEC) hyperplasia is associated with chronic lung diseases in humans, where it is thought to play a role in reparative responses to lung injury. To investigate the kinetics of strongly induced PNEC hyperplasia in an animal model, we exposed hamsters to a combination of hyperoxia (60% O2) and diethylnitrosamine (DEN) for up to 20 weeks. We thus demonstrate not only the induction but also spontaneous regression of intense PNEC differentiation and growth, which are much more intense than those observed with DEN alone. Lung tissues were immunostained for serotonin, calcitonin gene-related peptide (CGRP), calcitonin (CT), and gastrin-releasing peptide (GRP) (mammalian bombesin). Between 9 and 12 weeks of treatment, the number of CGRP- and serotonin-positive neuroepithelial bodies per cm airway epithelium increased over 10-fold, and CT became detectable. The number of neuroepithelial bodies immunostained for CGRP, serotonin, and CT peaked at 12-14 weeks of treatment, thereafter regressing to near-control levels by 20 weeks, in spite of continued DEN/O2 treatment. Simultaneously, by 6-7 weeks of treatment, there was a significant increase in the mean number of CGRP-positive cells per neuroepithelial body, which continued to rise up to double control levels, with a plateau at 13-20 weeks. GRP and pro-GRP immunostaining were not detectable at any time point. Polymerase chain reaction analyses of neuroendocrine-specific mRNAs demonstrated that CGRP, CT, and GRP mRNAs (normalized for beta-actin) peaked in lung tissues from most animals at 9-14 weeks after the beginning of DEN/O2 treatment, with decreased expression at 16-20 weeks. These data suggest that regulation of levels of these neuropeptides may be primarily transcriptional. This model may be a valuable system for analyzing mechanisms of induction and regression of normal PNEC differentiation and growth.
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PMID:Induction and spontaneous regression of intense pulmonary neuroendocrine cell differentiation in a model of preneoplastic lung injury. 131 33

Hyperoxia induces the expression of the hemopexin (Hx) gene in the liver in vivo. To investigate whether the Hx gene is activated by oxygen as such or via H2O2 as an oxygen signal transmitter the effects of arterial and venous O2 tensions as well as different concentrations of H2O2 on Hx mRNA expression were studied. After preculturing primary rat hepatocytes for 24 h at arterial O2 (16%) Hx mRNA was expressed with a maximal level (= 100%), when arterial O2 tension proceeded for 2 h, and to values of approximately 50%, when venous O2 tension (8%) proceeded for 2 h. When hepatocytes were precultured for 24 h under venous O2, Hx mRNA was induced by arterial O2 to values of 60% and under venous O2 to values of approximately 35%. The expression of beta-actin remained unchanged under arterial and venous O2. Exposure of hepatocyte cultures to H2O2 decreased the expression of Hx mRNA in a dose-dependent manner after 2 h, while heme oxygenase-1 (HO-1) mRNA was induced 2.5 fold. The results suggest that O2 per se rather than the reactive oxygen intermediate H2O2 modulates Hx expression.
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PMID:Modulation of hemopexin gene expression by physiological oxygen tensions in primary rat hepatocyte cultures. 764 92

The direct effects of hyperoxia on collagen production by fetal lung fibroblasts are unknown and would be important to the understanding of the molecular mechanisms involved in bronchopulmonary dysplasia in premature infants. We studied the effect of hyperoxia on 1) proliferation, 2) mRNA levels for type I and III procollagens, and 3) net collagen production in primary cultures of fetal rat lung fibroblasts. Fibroblasts from 19-day-old rat fetuses (term is 22 days) were obtained. Test plates were incubated in hyperoxia and controls in room air for varying time periods. Cell viability in both conditions was >97% as determined by trypan blue exclusion. Fibroblast proliferation in nonconfluent cultures was found to be significantly reduced with exposure to hyperoxia (P < 0.001). Steady-state levels of type I and III procollagen mRNAs, analyzed on Northern blots hybridized to [32P]cDNA probes, were significantly decreased in hyperoxia (P < 0.01). This effect was noted as early as 4 h of exposure to hyperoxia and persisted for 5 days. There was a significant inverse correlation between duration of exposure to O2 and steady-state levels of mRNA for alpha1(I)-procollagen (r = -0.904) and alpha1(III)-procollagen (r = -0.971). There were no significant changes in steady-state levels of beta-actin mRNA. We also found a significant decrease in collagen synthesis in hyperoxia-exposed fibroblasts (P < 0.05). We conclude that hyperoxia directly effects a reduction in fetal lung fibroblast proliferation and net collagen production at a pretranslational level.
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PMID:Hyperoxia inhibits fetal rat lung fibroblast proliferation and expression of procollagens. 935 46

Although a role for antioxidant enzymes in preventing lung injury from hyperoxic exposure has been implicated in a number of early studies, a direct test for the hypothesis was not available. We intended to address this question using genetically modified mice in which the expression of a single antioxidant enzyme was either enhanced or diminished. We reasoned that if an antioxidant enzyme functions in protecting lung cells against oxidant-mediated injury, the level of its gene expression would correlate with the degree of tolerance to hyperoxia. Overexpression of functional human manganese superoxide dismutase (MnSOD) in lung alveolar type I and type II cells, fibroblasts, and capillary endothelial cells in strain B6C3 mice was achieved by incorporating a human beta-actin promoter-based MnSOD transgene into the mouse genome. However, MnSOD overexpression failed to prolong the survival of transgenic mice on exposure to greater than 99% oxygen compared with wild-type mice. In addition, mice deficient in copper-zinc superoxide dismutase or cellular glutathione peroxidase exhibited a marked sensitivity to numerous models of oxidant tissue injury but were not hypersensitive to hyperoxia. These data suggest that the role of these three antioxidant enzymes in preventing oxidant-mediated lung injury from hyperoxic exposure is negligible, and other cellular antioxidant enzymes and systems may be primarily used by the lungs in defense against hyperoxia.
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PMID:Transgenic and knockout models for studying the role of lung antioxidant enzymes in defense against hyperoxia. 1247 Oct 89

Bolstering the endogenous oxidative damage defense system is a good strategy for development of treatments to combat neurodegenerative diseases in which oxidative damage plays a role. A first step in such treatment development is to determine the role of various components of the defense system in cells that degenerate. In this study, we sought to determine the role of superoxide dismutase 1 (SOD1) in two models of oxidative damage-induced retinal degeneration. In one model, paraquat is injected into the vitreous cavity and then enters retinal cells and generates reactive oxygen species (ROS) that cause progressive retinal damage. Assessment of retinal function with serial electroretinograms (ERGs) showed that sod1 -/- mice were much more sensitive than sod1 +/+ mice to the damaging effects of paraquat, while sod1 +/- mice showed intermediate sensitivity. Compared to sod1 +/+ mice, sod1 -/- mice showed greater paraquat-induced oxidative damage and apoptosis. In the second model, mice were exposed to hyperoxia for several weeks, and sod1 -/- mice showed significantly greater reductions in ERG amplitudes than sod1 +/+ mice. In both of these models, transgenic mice carrying a sod1 transgene driven by a beta-actin promoter showed less oxidative stress-induced reduction in ERG amplitudes. These data demonstrate that SOD1 protects retinal cells against paraquat- and hyperoxia-induced oxidative damage and suggest that overexpression of SOD1 should be considered as one component of ocular gene therapy to prevent oxidative damage-induced retinal degeneration.
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PMID:Superoxide dismutase 1 protects retinal cells from oxidative damage. 1674 61

The focus of this work was to elucidate the mechanism for inhibition of neutrophil beta(2) integrin adhesion molecules by hyperoxia. Results demonstrate that exposure to high oxygen partial pressures increases synthesis of reactive species derived from type 2 nitric-oxide synthase and myeloperoxidase, leading to excessive S-nitrosylation of beta-actin and possibly profilin. Hyperoxia causes S-nitrosylation of the four cysteine moieties closest to the carboxyl-terminal end of actin, which results in formation of short actin filaments. This alters actin polymerization, network formation, and intracellular distribution, as well as inhibits beta(2) integrin clustering. If neutrophils are exposed to ultraviolet light to reverse S-nitrosylation, or are incubated with N-formyl-methionyl-leucine-phenylalanine to trigger "inside-out" activation, the effects of hyperoxia are reversed. We conclude that cytoskeletal changes triggered by hyperoxia inhibit beta(2) integrin-dependent neutrophil adhesion.
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PMID:Actin S-nitrosylation inhibits neutrophil beta2 integrin function. 1828 5

Solea senegalensis is a commercial flat fish traditionally farmed in earth ponds in coastal wetlands that might also become important to more intensive aquaculture. Gas bubble disease (GBD) is a potential risk for outdoor fish farming, particularly in certain periods of the year, related to improper management leading to macroalgae blooms. Physical-chemical conditions inducing hyperoxia, including radiation, temperature, and high levels of dissolved oxygen, have been monitored in fish affected by GBD together with observed symptoms. Exophthalmia, subcutaneous emphysemas, obstruction of gill lamellae, hemorrhages, and anomalous swimming were the main effects of oxygen supersaturation. A proteomic study was carried out for the first time under aquaculture conditions and protein expression changes are described for fish that were subject to hyperoxic conditions. Proteins identified in gill of GBD-affected fish are related to oxidative alteration of cytoskeleton structure/function (beta-tubulin, beta-actin), motility (light myosin chain, alpha-tropomyosin), or regulatory pathways (calmodulin, Raf kinase inhibitor protein), reflecting the central role of gill in oxygen exchange. Hepatic proteins identified are related to protein oxidative damages (beta-globin, FABPs), protection from oxidative stress (DCXR, GNMT), and inflammatory response (C3), in agreement with the predominant metabolic role of liver. Comparison of protein expression patterns and protein identification are suggested as potentially specific hyperoxia biomarkers that would facilitate prevention of GBD outbreaks.
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PMID:Proteomics of juvenile senegal sole (Solea senegalensis) affected by gas bubble disease in hyperoxygenated ponds. 1910 63