Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although catalase is a major intracellular antioxidant, the expression of the human catalase gene appears to be limited in the airway epithelium, making these cells vulnerable to oxidant stress. The basis for this limited gene expression was examined by evaluation of the expression of the endogenous gene in human bronchial epithelial cells in response to hyperoxia. Hyperoxia failed to upregulate endogenous catalase gene expression, in contrast to a marked increase in expression of the heat shock protein gene. Sequence analysis of 1.7 kb of the 5'-flanking region of the human catalase gene showed features of a "house-keeping" gene (no TATA box, high GC content, multiple CCAAT boxes, and transcription start sites). Transfection of human bronchial epithelial cells with fusion genes composed of various lengths of the catalase 5'-flanking region and luciferase as a reporter gene showed low level constitutive promoter activity that did not change after exposure to hyperoxia. Importantly, using a replication-deficient recombinant adenoviral vector containing the human catalase cDNA, levels of catalase were significantly increased in human airway epithelial cells and this was associated with increased survival of the cells when exposed to hyperoxia. These observations provide a basis for understanding the sensitivity of the human airway epithelium to oxidant stress and a strategy for protecting the epithelium from such injury.
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PMID:Vulnerability of the human airway epithelium to hyperoxia. Constitutive expression of the catalase gene in human bronchial epithelial cells despite oxidant stress. 828

Exposure to high partial pressures of oxygen are toxic to the lung, and much of the damage observed is related to injury of the pulmonary microvasculature. In this study, we evaluated the response of the pulmonary microvascular endothelial cell to high oxygen concentrations, using two-dimensional protein gel electrophoresis as a direct molecular assay of differences between cells exposed to room air or hyperoxia. We observed a differential expression of five specific proteins within 24 h of a hyperoxic insult that we termed hyperoxia-responsive proteins. After 4 h of hyperoxia there was a decrease in two of the proteins. From 8 to 24 h we observed a repression of a third and an induction of the other two proteins. One of the induced proteins was also increased by heat shock and hydrogen peroxide and has characteristics similar to heat shock protein (HSP) 32 (heme oxygenase 1). Western analysis using an antibody specific to rat heme oxygenase 1 verified that this oxygen-responsive protein is heme oxygenase 1. The response of the other four hyperoxia-responsive proteins appears to be specific to oxygen and not a general stress response, since they were not changed in response to heat shock or hydrogen peroxide. Based on RNA inhibitor and pulse chase experiments, these changes may result from transcriptional/posttranscriptional mechanisms or hyperoxia-dependent protein turnover.
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PMID:Hyperoxia-responsive proteins in rat pulmonary microvascular endothelial cells. 892 10

To understand the molecular mechanisms that upregulate the activities of pulmonary antioxidant enzymes in adult rats during exposure to 85% oxygen, the relative contents of corresponding mRNA in normal and hyperoxic lungs were determined. Hyperoxic exposure drastically induced the expression of lung manganese-containing superoxide dismutase (MnSOD) mRNA. Maximal induction of MnSOD mRNA occurred at days 3 and 5 of exposure to hyperoxia, reaching a 600 and a 340% increase over the levels of air-exposed rats, respectively. In addition, hyperoxia induced lung mRNA for glucose-6-phosphate dehydrogenase, glutathione peroxidase, glyceraldehyde-3-phosphate dehydrogenase, alpha-tubulin, and gamma-actin to different extends at various days of exposure. Hyperoxia had little or no effect on the levels of mRNA for copper/zinc-containing superoxide dismutase (CuZnSOD), catalase, heat shock protein (HSP70), and creatine kinase. Nuclear run-on experiments showed that the transcriptional rate of the MnSOD gene is enhanced in hyperoxic rat lungs by approximately 400% at day 3 of exposure compared with that of controls. The specific activities of CuZnSOD and MnSOD in these lung samples per unit of lung protein or DNA were also determined. The activity of CuZnSOD in hyperoxic lungs was found to be unchanged compared with controls, except a 20% decrease at day 7 of exposure when standardized against protein content of lung homogenate. Changes of CuZnSOD activity were more dramatic in hyperoxic lungs (a 40% increase at days 3, 5, 7, and 14 of exposure) when enzyme activity was normalized using lung DNA content. Surprisingly, no proportional increase of lung MnSOD enzyme activity was observed at days 3 and 5 of oxygen exposure. The increase of MnSOD activity per unit of lung protein also did not parallel the increase in MnSOD protein content at days 5, 7, and 14 of exposure. These data suggest that, in addition to transcriptional activation, translational and/or posttranslational regulation of the MnSOD gene expression may play a critical role in controlling lung MnSOD activity on hyperoxic exposure.
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PMID:Antioxidant enzyme expression in rat lungs during hyperoxia. 896 16

Recent studies suggest that normobaric hyperoxia can be beneficial, if administered during transient stroke. However, increased oxygenation theoretically may increase oxygen free-radical injury, particularly during reperfusion. In the present study, the authors assessed the benefit and risks of hyperoxia during focal cerebral ischemia and reperfusion. Rats were subjected to hyperoxia (Fio2 100%) or normoxia (Fio2 30%) during 2-hour filament occlusion and 1-hour reperfusion of the middle cerebral artery. At 24 hours, the hyperoxia group showed 70% (total) and 92% (cortical) reduction in infarct volumes as compared to the normoxia group. Levels of oxidative stress were evaluated using three indirect methods. First, since oxygen free radicals increase blood-brain barrier (BBB) damage, Evan's blue dye extravasation was quantified to assess BBB damage. Second, the expression of heme oxygenase-1 (HO-1), a heat shock protein inducible by oxidative stress, was assessed using Western blot techniques. Third, an immunoblot technique ("OxyBlot") was used to assess levels of protein carbonyl formation as a marker of oxidative stress-induced protein denaturation. At 24 hours, Evan's blue dye extravasation per average lesion volume was similar between groups. There were no significant differences in HO-1 induction and protein carbonyl formation between groups, in the ipsilateral or contralateral hemispheres, at 6 hours and at 24 hours. These results indicate that hyperoxia treatment during focal cerebral ischemia-reperfusion is neuroprotective, and does not increase oxidative stress.
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PMID:Effects of normobaric hyperoxia in a rat model of focal cerebral ischemia-reperfusion. 1214 71

Nuclear factor E2 p45-related factor 2 (NRF2) contributes to cellular protection against oxidative insults and chemical carcinogens via transcriptional activation of antioxidant/detoxifying enzymes. To understand the molecular basis of NRF2-mediated protection against oxidative lung injury, pulmonary gene expression profiles were characterized in Nrf2-disrupted (Nrf2(-/-)) and wild-type (Nrf2(+/+)) mice exposed to hyperoxia or air. Genes expressed constitutively higher in Nrf2(+/+) mice than in Nrf2(-/-) mice included antioxidant defense enzyme and immune cell receptor genes. Higher basal expression of heat shock protein and structural genes was detected in Nrf2(-/-) mice relative to Nrf2(+/+) mice. Hyperoxia enhanced expression of 175 genes (> or = twofold) and decreased expression of 100 genes (> or =50%) in wild-type mice. Hyperoxia-induced upregulation of many well-known/new antioxidant/defense genes (e.g., Txnrd1, Ex, Cp-2) and other novel genes (e.g., Pkc-alpha, Tcf-3, Ppar-gamma) was markedly greater in Nrf2(+/+) mice than in Nrf2(-/-) mice. In contrast, induced expression of genes encoding extracellular matrix and cytoskeletal proteins was higher in Nrf2(-/-) mice than in Nrf2(+/+) mice. These NRF2-dependent gene products might have key roles in protection against hyperoxic lung injury. Results from our global gene expression profiles provide putative downstream molecular mechanisms of oxygen tissue toxicity.
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PMID:Gene expression profiling of NRF2-mediated protection against oxidative injury. 1562 62

1. Glutamine is an amino acid that is used to treat various diseases. Glutamine has been reported to have protective effects in human pulmonary epithelia-like cells exposed to hyperoxia. However, the effects of glutamine in hyperoxia-induced lung injury have not been investigated in vivo. 2. Mice treated with saline or glutamine [(750 mg/kg) intravenously] were randomly exposed to hyperoxia for 48 or 72 h. Control mice treated with saline or glutamine were exposed to room air. Cytokine levels in bronchoalveolar lavage fluid (BALF), heat shock protein (HSP) 70, the wet/dry (W/D) weight ratio, malondialdehyde (MDA) levels, myeloperoxidase (MPO) activity and pathoglogical findings in lung tissue were evaluated to determine the effects of glutamine on acute lung injury. In addition, survival was monitored. 3. Lung expression of HSP70 was significantly enhanced in both the control (room air) and 48 and 72 h hyperoxic glutamine-treated mice. The W/D ratio, BALF concentrations of tumour necrosis factor-alpha and interleukin-6, MDA levels, MPO activity, neutrophil infiltration and interstitial oedema in lung tissue were significantly lower at 48 and 72 h of hyperoxia in glutamine-treated mice compared with saline-treated mice. 4. In a separate series of experiments evaluating survival, after 96 h continuous exposure to hyperoxia, all saline-treated mice died. In contrast, all glutamine-treated mice died after 108 h exposure to hyperoxia. 5. The data suggest that glutamine administered to mice during hyperoxia has a protective effect against hyperoxia-induced acute lung injury and improves survival.
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PMID:Glutamine attenuates hyperoxia-induced acute lung injury in mice. 1956 32

Gene expression changes in response to aging, heat stress, hyperoxia, hydrogen peroxide, and ionizing radiation were compared using microarrays. A set of 18 genes were up-regulated across all conditions, indicating a general stress response shared with aging, including the heat shock protein (Hsp) genes Hsp70, Hsp83 and l(2)efl, the glutathione-S-transferase gene GstD2, and the mitochondrial unfolded protein response (mUPR) gene ref(2)P. Selected gene expression changes were confirmed using quantitative PCR, Northern analysis and GstD-GFP reporter constructs. Certain genes were altered in only a subset of the conditions, for example, up-regulation of numerous developmental pathway and signaling genes in response to hydrogen peroxide. While aging shared features with each stress, aging was more similar to the stresses most associated with oxidative stress (hyperoxia, hydrogen peroxide, ionizing radiation) than to heat stress. Aging is associated with down-regulation of numerous mitochondrial genes, including electron-transport-chain (ETC) genes and mitochondrial metabolism genes, and a sub-set of these changes was also observed upon hydrogen peroxide stress and ionizing radiation stress. Aging shared the largest number of gene expression changes with hyperoxia. The extensive down-regulation of mitochondrial and ETC genes during aging is consistent with an aging-associated failure in mitochondrial maintenance, which may underlie the oxidative stress-like and proteotoxic stress-like responses observed during aging.
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PMID:Gene expression changes in response to aging compared to heat stress, oxidative stress and ionizing radiation in Drosophila melanogaster. 2321 61