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

We previously demonstrated that hyperoxia-exposed immature rats develop airway smooth muscle layer thickening; this remodeling appears partially attributable to smooth muscle hyperplasia. In this study, we tested the hypothesis that excess mitogenic activity for airway smooth muscle cells is present within the lungs of hyperoxia-exposed immature rats. We assessed the proliferative effect of bronchoalveolar lavage (BAL) fluid from air- and O2-exposed animals on cultured rat tracheal smooth muscle cells. BAL fluids from air- or O2-exposed immature rats increased DNA synthesis ([3H]-thymidine incorporation at 24 h of incubation) and cell number (compared with DMEM-treated control cells, at 2 days of incubation), but BAL fluid from O2-exposed animals had significantly greater mitogenic effects. This excess mitogenic activity was lipid inextractable and was ablated by trypsin digestion, indicating that at least one polypeptide growth factor was responsible; molecular sieve fractionation demonstrated a molecular weight of > 10 kD. Because platelet-derived growth factor (PDGF) has been identified in other models of hyperoxia exposure, we tested the further hypothesis that PDGF contributes to the observed excess mitogenic activity. Addition of neutralizing anti-PDGF antibodies to BAL-stimulated smooth muscle cultures did not reduce BAL fluid-induced mitogenesis. These data indicate that the lungs of O2-exposed rats contain excess mitogenic activity for airway smooth muscle, attributable to non-PDGF polypeptide growth factors. It is conceivable that this abnormal mitogenic activity contributes to O2-induced airway smooth muscle remodeling observed in immature rats in vivo.
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PMID:Bronchoalveolar lavage fluid from immature rats with hyperoxia-induced airway remodeling is mitogenic for airway smooth muscle. 787 92

The objective of this study was to explore the relationship between oxidative molecular damage and the aging process by determining whether such damage is associated with the rate of aging, using the adult housefly as the experimental organism. Because the somatic tissues in the housefly consist of long-lived postmitotic cells, it provides an excellent model system for studying cumulative age-related cellular alterations. Rate of aging in the housefly was manipulated by varying the rate of metabolism (physical activity). The concentration of 8-hydroxydeoxyguanosine (80HdG) was used as an indicator of DNA oxidation. Exposure of live flies to x-rays and hyperoxia elevated the level of 8OHdG. The level of 8OHdG in mitochondrial as well as total DNA increased with the age of flies. Mitochondrial DNA was 3 times more susceptible to age-related oxidative damage than nuclear DNA. A decrease in the level of physical activity of the flies was found to prolong the life-span and corresponding reduce the level of 8OHdG in both mitochondrial and total DNA. Under all conditions examined, mitochondrial DNA exhibited a higher level of oxidative damage than total DNA. The 8OHdG levels were found to be inversely associated with the life expectancy of houseflies. The pattern of age-associated accrural of 8OHdG was virtually identical to that of protein carbonyl content. Altoghether, results of this study support the hypothesis that oxidative molecular damage is a causal factor in senescence.
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PMID:DNA oxidative damage and life expectancy in houseflies. 799 27

Exposure of 21-day-old Sprague-Dawley rats to hyperoxia (> 95% O2 for 8 days) causes thickening of the airway epithelial and smooth muscle layers. To test the hypothesis that hyperoxic exposure increases airway layer DNA synthesis, we labeled the nuclei of cells undergoing S-phase by administering the thymidine analog bromodeoxyuridine (BrdU). BrdU was administered on days 3 and 4, 5 and 6, or 7 and 8 of air or O2 exposure, and the lungs were harvested immediately thereafter. Histologic sections were stained with an avidin-biotin-immunoperoxidase stain that revealed BrdU incorporation into nuclei, and a hematoxylin counterstain. After 4 days of air or O2 exposure, there was no difference in BrdU fractional labeling between control and hyperoxic animals. Thereafter, fractional BrdU labeling of the small airway (circumference < 1,000 microns) epithelium and smooth muscle layer was significantly increased in O2-exposed animals (P < 0.01, unpaired t test). The fractional labeling of larger, central airway smooth muscle layer cells was also increased after 8 days of O2 exposure (P < 0.01). In another cohort of O2-exposed animals, measurements of airway layer dimensions demonstrated increases in small airway epithelial and smooth muscle layer thickness that paralleled the time course seen for BrdU incorporation. We conclude that O2 exposure of immature rats increases airway epithelial and smooth muscle layer cellular DNA synthesis. These data suggest that hyperplasia of airway epithelial and smooth muscle layer cells may contribute to hyperoxia-induced airway remodeling.
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PMID:Hyperoxia increases airway cell S-phase traversal in immature rats in vivo. 808 67

Reactive oxygen species have been implicated in aerobic organisms as causative agents in damage to DNA, proteins, and lipids. Catalase is a major enzyme in the defense against such oxidant damage. To determine whether increased catalase expression confers greater resistance to oxidant stress, a eukaryotic expression vector harboring a human catalase cDNA clone was constructed. Acatalasemic murine fibroblasts were then co-transfected with that catalase expression vector and pSV2-neo, and successfully transfected cells were identified by their ability to grow in the presence of geneticin. Clones that contained integrated copies of the catalase expression vector were identified by Polymerase Chain Reaction (PCR) analysis. Stably transfected geneticin-resistant cell lines that overexpressed catalase in potentially positive cell lines were confirmed by catalase enzyme assays. To examine the physiological relevance of catalase overexpression, cells were exposed to oxidant stresses (hydrogen peroxide and hyperoxia), and survival rates were determined. Results demonstrated a significant resistance to oxidative stress in cells overexpressing catalase when compared to controls. These transfected cell lines will provide important models for further evaluation of the role of catalase in protecting cells against the toxic effects of oxygen-derived free radicals and their derivatives.
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PMID:Expression of human catalase in acatalasemic murine SV-B2 cells confers protection from oxidative damage. 813 83

Exposure of cell cultures to hyperoxia, i.e., an atmosphere containing more than 20% O2, results in various genotoxic effects. The most prominent effect of hyperoxia is its clastogenicity. In this paper, earlier published data, obtained from research devoted to the mechanism of hyperoxia-induced clastogenesis, are reviewed. In addition, new data are presented concerning the hyperoxia-sensitivity of the DNA-repair deficient Chinese hamster cell lines xrs1, irs1, and EM9. None of these ionizing radiation-sensitive mutants showed hypersensitivity to hyperoxia, as measured by chromosomal aberration induction and loss of clonogenic cell survival. From the normal hyperoxia-sensitivity of xrs1, it may be concluded that DNA double strand breaks, of the type that are induced by ionizing radiation, do not play a role in chromosomal aberration formation by hyperoxia. In addition, since xrs1 is hypersensitive to drugs that inhibit topoisomerase II, it seems rather unlikely that exposure to hyperoxia affects topoisomerase II activity. Based on circumstantial evidence we hypothesize that perturbation of poly(ADP-ribose) metabolism may play a critical role in the mechanism of hyperoxia-induced clastogenesis.
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PMID:Mechanism of hyperoxia-induced chromosomal breakage in Chinese hamster cells. 822 8

The effect of hyperoxia (O2 > 95%) for 48 hours on the induction of pulmonary and hepatic cytochrome P450 has been investigated in adult male rats. Northern blot analysis using six "specific" oligonucleotide probes indicated that CYP 1A1 and CYP 1A2 mRNAs in liver and CYP 1A1 mRNA in lung were significantly increased by hyperoxic exposure, whereas the major constitutive P450 mRNAs, CYP 2C11 in liver and CYP 2B1 in lung, were decreased. Since induction of CYP 1A1 has only been reported with the use of exogenously administered xenobiotics, further studies were carried out to confirm the results obtained with Northern blot analysis. cDNAs were synthesized for CYP 1A1 and 1A2 in the liver and CYP 1A1 in the lungs and amplified by reverse PCR. These results indicate that these cDNAs were amplified significantly more in the hyperoxia group than in the control animals. Futhermore, CYP 1A1 and 1A2 proteins in liver and CYP 1A1 protein in lungs as well as the corresponding monooxygenase activities were increased by hyperoxia. Hyperoxic induction of CYP 1A1 and 1A2 is the first demonstration of nonexogenous CYP 1A induction in animals and indicates the needs to pursue the changes of Ah receptor-ligand-DNA interaction in hyperoxia.
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PMID:Induction of cytochrome P450 1A1 and 1A2 by hyperoxia. 826 28

Oxygen therapy in preterm infants is associated with bronchopulmonary dysplasia, but the relative importance of oxygen toxicity as compared to adverse effects of intubation and mechanical ventilation, remains uncertain. In freely-breathing neonatal rats, exposure to 100% oxygen for as little as 2 hr produced a significant reduction in lung DNA synthesis, evaluated by [3H]thymidine incorporation, without a concomitant effect on [3H]leucine incorporation into protein. These results indicate that hyperoxia has a selective deleterious effect on mitosis in developing lung.
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PMID:Immediate decline in DNA synthesis in neonatal rat lung caused by exposure to 100% oxygen. 835 12

We assessed the mechanics and morphology of the lung in 165 rats treated neonatally with either room air (RA), O2, RA + steroids, or O2 + steroids. Newborn Sprague-Dawley male rats were randomly assigned to these groups. O2-exposure (0.96-1.0 FiO2) lasted 5 days, and dexamethasone treatment consisted of eight daily S.C. injections of drug or buffer in successive doses of 0.5, 0.4, 0.3, 0.2, 0.1, 0.1, 0.1, and 0.1 mg/kg. At 58 days, right ventricular systolic pressure (RVP) was measured. At 60 days, all rats were sacrificed for obtaining lung weight and DNA, saline pressure-volume (P-V) curves, and morphometry. We weighted right ventricles (RV) and left ventricles + septa (LV). Hyperoxia alone did not, but steroid decreased survival rate to 79.4% (95.3% in RA rats, P < 0.02). Only 21 of 40 (52%) O2 + steroids rats survived, less than in both RA groups (P < 0.001). RV weight, RVP and muscularization of alveolar duct arteries were significantly increased in O2 vs. RA rats. In RA + steroids rats, weight of the LV was decreased but RV, RVP, and lung vasculature were not affected. These effects were additive in the O2 + steroid group. Wet lung weights and DNA were increased for RA + steroid rats over all others. O2 and steroids shifted the P-V curve to the left and O2 + steroids still further. Maximal lung volume increased significantly with RA + steroids and still further in O2 + steroids but not in O2 alone. O2 and steroids significantly increased the mean linear intercept and O2 + steroids even more so.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chronic modifications of lung and heart development in glucocorticoid-treated newborn rats exposed to hyperoxia or room air. 836 21

A broad array of oxidative stresses modulates gene expression in a variety of mammalian cells. One goal of this review was to characterize cellular responses to oxidative injury, how these processes are regulated, and the outcome for a particular cell or tissue. Many genes induced in response to specific oxidant stresses have been identified and include transcription factors, replication proteins, proteases, protease inhibitors, proteins affecting cell proliferation and various antioxidants, i.e. heme oxygenase, MT, and MnSOD. The latter enzyme is induced after a number of cytokines and oxidant stresses including hyperoxia and mineral dusts causing inflammation. Moreover, increases in mRNA levels of TNF and IL-1, cytokines inducing MnSOD, are observed after exposure to UV and ionizing radiation. Since increased electron flow could lead to generation of more AOS within mitochondria, increased levels of MnSOD might be necessary to maintain normal functioning of the mitochondria after oxidative stress. Alterations in cell growth are intrinsically related to the pathogenesis of many diseases. Paradoxically, some of the responses of cells to oxidative stress reflect cytotoxicity and cytostasis, whereas others result in increased cell proliferation. For example, induction of gadd genes observed after oxidative stress is related to growth arrest of cells, a response which might enable the cell to repair oxidative damage prior to replication. This phenomenon might prevent fixation of mutations associated with oxidative DNA damage. On the other hand, increased mRNA expression and activity of ODC, observed after exposure of cells to UV or asbestos is associated with increased cell proliferation. In addition, increased mRNA expression of cellular proto-oncogenes observed after exposure to oxidants could also be related to increased DNA synthesis or proliferation. Figure 5 provides a general scheme of cell responses to oxidative stress and possible ramifications. AOS can react with a number of target molecules including proteins, lipids, and DNA. These interactions elicit a number of signals including activation of gene regulatory factors (transcription factors) which in turn activate oxidative stress-responsive genes or regulons. Consequently, a number of proteins are produced with distinctive functions including DNA repair enzymes, antioxidants, proteases inhibitors, cytokines and proteins affecting cell proliferation. These cellular responses to AOS can lead to restoration of normal cellular function and adaptation to oxidative stress, cell death or aberrant proliferation. It is the latter two responses which can lead to a variety of disease states including cancer.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cell and tissue responses to oxidative damage. 837 69

There is mounting evidence on the role of oxygen-derived free radicals in causing damage to various cellular components. However, most studies reported in the literature have been conducted under conditions where cells were challenged with chemical free radical generating systems. In contrast, we measured DNA strand breaks, through a relatively simple and sensitive technique, as a function of the dissolved oxygen tension in a bioreactor. Cells were exposed to a step change in oxygen tension at mid-exponential growth phase. Several levels of oxygen were tested (200, 300, and 476% dissolved oxygen with respect to air saturation at 1 atmosphere) and compared against a control (10% dissolved oxygen). Hyperoxia was found to cause monotonically increasing DNA strand breakage at all the oxygen levels. In addition, hyperoxia was found to affect other metabolic functions such as the glucose consumption rate, lactate production rate, and cell growth. When hyperoxia-induced DNA strand breakage was compared to that induced by exposure to hydrogen peroxide, a similar response was observed. Exposure to a dissolved oxygen level of 200% induced DNA strand breakage comparable to a bolus of 4.2 microM hydrogen peroxide. Our results show that there is an association between hyperoxia and DNA damage.
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PMID:Hyperoxia induces DNA damage in mammalian cells. 845 84


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