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

In this study, we have used the rat model of hyperoxia to examine the molecular responses to oxidative stress in lung. We show that in addition to the antioxidant enzyme manganese superoxide dismutase, expression of a variety of stress-responsive genes including heme oxygenase-1, c-fos, c-jun, CAAT-enhancer binding protein (C/EBP)-beta, and C/EBP-delta were increased after hyperoxia. Increased c-fos, c-jun, C/EBP-beta, and C/EBP-delta mRNA expression was correlated with increased DNA binding activity of the transcription factor complexes activator protein 1 and C/EBP in tissue lysates. Because oxidative damage plays an important role in the aging process and little is known about the susceptibility of aged rats to hyperoxia, we also examined the relative tolerance of old rats to hyperoxia. Surprisingly, we observed that aged rats exhibit greater tolerance to hyperoxic stress than young rats. Old rats exhibited decreased arterial oxygen tension when compared to young rats after hyperoxia exposure. This increased tolerance coincided with decreased albumin levels in bronchoalveolar lavage and the delayed onset of activation of transcription factors and expression of oxidative stress-inducible genes in old rats. Transcription factor and stress-response gene activation may serve as useful molecular markers for oxidant lung injury.
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PMID:Molecular responses to hyperoxia in vivo: relationship to increased tolerance in aged rats. 759 40

Heme oxygenase 1 (HO-1), a stress response protein, is highly induced in response to various agents causing oxidative stress including ultraviolet irradiation, sodium arsenite, hyperoxia, and glutathione depletors. We recently characterized the induction of HO-1 gene expression by nitric oxide (NO) and postulated that the addition of an antioxidant, such as pyrrolidine dithiocarbamate (PDTC), would attenuate HO-1 induction in response to NO. Surprisingly, PDTC was a very potent inducer of HO-1 gene expression, causing increases in the steady-state level of HO-1 mRNA in rat aortic vascular smooth muscle (aVSM) cells in a time- and concentration-dependent manner. PDTC-induced HO-1 gene expression correlated with a rise in protein levels and was dependent on both increased gene transcription and mRNA stability. Deletional analyses of the proximal promoter and the entire 5' distal upstream region of the HO-1 gene (11 kbp) were performed including the two 5' distal enhancers, SX2 and AB1, located 4 kbp and 10 kbp upstream of the transcription site, respectively. Plasmid vectors containing various fragments of this region were linked to a chloramphenicol acetyl transferase (CAT) reporter gene, stably transfected into RAW 264.7 cells, and transfectants were assayed for CAT activity after treatment with PDTC. We show that the AB1 distal enhancer plays an important role in mediating PDTC-induced HO-1 gene transcription. Mutational analyses of this enhancer showed that the activator protein 1 (AP-1) regulatory element is crucial for PDTC-induced HO-1 gene transcription. Electrophoretic mobility shift assays supported this data, demonstrating increased AP-1 DNA binding activity after PDTC treatment. Taken together, our data demonstrate that the antioxidant PDTC enhances HO-1 gene transcription and that the induction appears to be mediated by AP-1 activation of regulatory elements specific to the distal enhancer AB1.
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PMID:Transcriptional regulation of the heme oxygenase 1 gene by pyrrolidine dithiocarbamate. 983 57

Apoptosis has been hypothesized to be mediated through the induction of free radicals via oxidative pathway. In this study, we demonstrated the induction of cellular apoptosis by anoxia-hyperoxia shift, but not by anoxia or hyperoxia alone in NIH3T3 cells. The decrement of ROS by anoxia thus appears to be an essential early event leading to apoptosis. G1 arrest was detected in anoxia-treated cells, and postanoxic oxygen recovery could reverse this effect, and induce apoptosis. On analysis of the binding activity of AP-1, we found biphasic induction of binding ability in cells undergoing anoxia-hyperoxia shift. In the early stage of anoxia, a transitional increase of AP-1 binding activity was detected, which was reduced to the minimal levels after 24 h of anoxia. During the period of postanoxic hyperoxia treatment, the binding activity of AP-1 was reinduced and increased remarkably with time up to 24 h. These results were in accordance with the expressions of c-jun and c-fos proteins. Enhancement of poly(ADP-ribosyl)ation activities, especially ADP-ribosylation of histone H1 was detected in post-anoxic hyperoxia-treated cells, and cleavage of PARP and activation of caspase 3 were also observed in post-anoxic hyperoxia (recovery) treated cells, but not in anoxia-treated cells. We propose that the differential induction of c-jun/c-fos (AP-1) gene expressions and sequential activation of PARP activity are essential in anoxia/hyperoxia-induced apoptosis.
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PMID:Elevation of apoptotic potential by anoxia hyperoxia shift in NIH3T3 cells. 1048 34

Immature organisms (neonates; <12 h old) have vastly differing responses to hyperoxic injury than adults. A common feature of hyperoxic gene regulation is involvement of activator protein (AP)-1. We evaluated lung AP-1 binding as well as that of the AP-1 subunit proteins c-Fos, c-Jun, phosphorylated c-Jun, Jun B, and Jun D after exposure to >95% O(2) for 3 days. Unlike adults, neonates showed no increased AP-1 binding in hyperoxia despite a high affinity of the AP-1 binding complexes for phosphorylated c-Jun and Jun D as demonstrated by supershift of these antibodies with the AP-1 complexes. Moreover, neonatal lungs exhibited two distinguishable AP-1 binding complexes, whereas adult lungs had one. In neonates, sequential immunoprecipitation revealed that the lower AP-1 complex was composed of proteins from both the Fos and Jun families, whereas the upper complex consisted of Jun family proteins, with predominance of Jun D. In adults, the single AP-1 complex appeared to involve other Fos or non-Fos or non-Jun family proteins as well. Neonatal lungs showed a higher level of Jun B and Jun D immunoreactive proteins in both air and hyperoxia compared with those in adult lungs. These results suggest that significant maturational differences in lung AP-1 complexes exist and that these may explain transcriptional differences in hyperoxic gene regulation.
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PMID:Maturational differences in hyperoxic AP-1 activation in rat lung. 1066 24

We have previously shown marked induction of the stress-inducible gene heme oxygenase-1 (HO-1) in vivo and in vitro after hyperoxia. In RAW 264.7 cells, HO-1 induction is transcriptionally regulated and dependent on cooperation between the HO-1 gene promoter and the 5' distal enhancer element SX2. In our present study, further deletional and mutational analyses demonstrate that signal transducer and activator of transcription (STAT) DNA binding sites located in the promoter of HO-1 and activator protein (AP)-1 DNA binding sites in the distal enhancer element SX2 are necessary for optimal HO-1 gene activation after hyperoxia. Interestingly, a second 5' distal enhancer element, AB1, located 10 kb upstream from the HO-1 promoter, alone is activated after hyperoxia but cannot confer maximal hyperoxia-induced HO-1 gene transcription. Mutational analysis of the AB1 enhancer shows that AP-1 is essential for AB1-mediated HO-1 gene transcription after hyperoxia. Electromobility shift assays show increased STAT1, STAT3, STAT5, and AP-1 DNA binding activity in RAW 264.7 cells after hyperoxia. Taken together, our data suggest that the 5' distal enhancer elements of the HO-1 gene in concert with the promoter regulate HO-1 gene induction and highlight the complexity of HO-1 gene transcription in response to hyperoxia.
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PMID:AP-1 and STAT mediate hyperoxia-induced gene transcription of heme oxygenase-1. 1089 16

The inducible nitric oxide (NO) synthase gene in alveolar macrophages (AMs) is a stress response gene that may contribute to tissue injury in the lung after respiration with high O(2) concentrations through extensive production of NO. In this study, we investigated the influence of hyperoxia on the NO pathway in rat AMs in vitro, its regulation by the transcription factors nuclear factor (NF)-kappaB and activator protein (AP)-1, and the role of reactive oxygen species (ROS). AMs were treated with lipopolysaccharide (LPS) and/or interferon (IFN)-gamma and incubated under 21 or 85% O(2). Stimulation with LPS and IFN-gamma led to induction of the NO pathway that was further upregulated by hyperoxia. The binding activity of NF-kappaB, in contrast to that of AP-1, was activated on stimulation with LPS and IFN-gamma, and both were further increased under hyperoxia. The antioxidants pyrrolidine dithiocarbamate and N-acetyl-L-cysteine inhibited intracellular ROS production and the NO pathway under both normoxic and hyperoxic conditions but had diverse effects on the transcription factors. The results presented here indicate that hyperoxia can upregulate the NO pathway in stimulated AMs through increased production of intracellular ROS and activation of NF-kappaB and AP-1.
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PMID:Hyperoxia upregulates the NO pathway in alveolar macrophages in vitro: role of AP-1 and NF-kappaB. 1129 May 14

The aged nervous system displays impaired cognitive functions, and these impairments are exacerbated in several neurodegenerative diseases. A role for oxidative stress has been suggested for several of these age-associated dysfunctions. In addition, recovery from more acute traumatic insults that also generate oxidative stress is impaired in the aged. Here we examine the response of aged rat hippocampi to normobaric hyperoxia treatments and demonstrate an attenuation in the DNA binding activity of the AP-1 and nuclear factor-kappa B transcription factors, which are important components of stress response signal transduction pathways and can determine shifts in cellular commitments to necrosis, apoptosis, or functional recovery in the central nervous system.
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PMID:Attenuated transcriptional responses to oxidative stress in the aged rat brain. 1239 91

Oxidative stress appears to contribute to neurodegenerative outcomes after ischemia, hypoxia, and hyperoxia. The AP-1 transcription factor is made up of a family of regulatory proteins that can be activated by oxidative stress. In the present study, we examined AP-1 DNA binding activity in terms of specific participating AP-1 proteins in rat brain after hyperoxia. Male Sprague-Dawley rats were exposed to 100% oxygen under isobaric conditions over time. The AP-1 DNA binding activity present in the rat hippocampus and basal forebrain was characterized by electrophoretic mobility shift analysis (EMSA) and the participating AP-1 proteins identified by immunodepletion/supershift and Western blotting analyses. The Fos and Jun proteins were localized by immunohistochemistry to hippocampus. There were significant increases in AP-1 DNA binding in both hippocampus and basal forebrain after hyperoxia. There was also a significant increase in c-Jun protein levels and the proportion of c-Jun present in AP-1 DNA binding complexes in hippocampal nuclei after hyperoxia. These results suggest that AP-1 activation via c-Jun binding to DNA is an important component of brain responses to oxidative stress.
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PMID:Hyperoxia increases AP-1 DNA binding in rat brain. 1258 69

Administration of high concentrations of oxygen (hyperoxia) is a mainstay of supportive treatment for patients suffering from severe respiratory failure. However, hyperoxia, by generating excess systemic reactive oxygen species (ROS), can exacerbate organ failure by causing cellular injury. Therefore, a better understanding of the signal transduction pathways in hyperoxia may provide the basis for effective therapeutic interventions. The major biological effects of hyperoxia include cell death, induction of stress responses, inflammation, and modulation of cell growth. Major signaling pathways that appear to be involved include the mitogen-activated protein kinases (MAPKs), AP-1, and NF-kappa B, which converge, ultimately, to the expression of a range of stress response genes, cytokines, and growth factors.
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PMID:Pathways of cell signaling in hyperoxia. 1289 37

The alveolar macrophage is an important source of interleukin (IL)-8 during pulmonary injury. The IL-8 gene promoter sequence contains nuclear factor (NF)-kappa B, NF-IL6, and activator protein (AP)-1 binding sequences. These sites may have differing regulatory roles in hyperoxia-exposed macrophages than in those stimulated by bacterial lipopolysaccharide (LPS). U-937 and THP-1 macrophage-like cells were exposed to air-5% CO2 or 95% O2-5% CO2, with or without 1.0 microg/ml of LPS, and transfected with an IL-8 promoter-reporter containing NF-kappa B, NF-IL6, or AP-1 mutations. Hyperoxia and LPS caused additive increases in IL-8 production by U-937 cells, whereas THP-1 cells responded only to LPS. An NF-kappa B mutation ablated baseline and O2- and LPS-stimulated reporter activity in both cell lines, whereas NF-IL6 mutations had little effect. An AP-1 mutation had an intermediate effect. LPS, but not hyperoxia, stimulated nuclear translocation of NF-kappa B in both cell lines. Pharmacological blockade of NF-kappa B nuclear translocation ablated LPS-, but not hyperoxia-, stimulated IL-8 production. Although an intact promoter NF-kappa B site is crucial to macrophage IL-8 production, only LPS-stimulated production appears to require additional nuclear translocation of NF-kappa B.
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PMID:Differential roles for NF-kappa B in endotoxin and oxygen induction of interleukin-8 in the macrophage. 1290 91


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