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

To examine the dose-response relationships of oxygen-induced lung changes, newborn rats were exposed to various patterns of concentrations of hyperoxia (0.4, 0.8, and greater than 0.95 FiO2) for up to 12 days. Prominent findings included microscopic evidence of lung injury and retarded alveolar development (secondary septal development delayed by as much as 88%), lower whole lung DNA (50% of control), lung-to-body-weight ratios (by as much as 18%), and significantly less compliance in the lungs afer exposures of 6 or 12 day duration to all concentrations of hyperoxia. Significant increases in the activities of the lung protective enzymes superoxide dismutase (129 to 160% of control), catalase (112 to 274% of control), and glutathione peroxidase (118 to 256% of control) were noted when activity was expressed on a DNA basis after 12 day exposures to the various patterns of hyperoxia. Lung changes noted after a 7-day recovery period in air included interstitial thickening (117% of control), persistance of the microscopic injury, and retarded alveolar development seen immediately after initial 6-day hyperoxic exposures. At the conclusion of a second wk of recovery in air, the lungs of hyperoxic exposed animals resembled controls in most respects, but a significantly altered compliance was exhibited by the lungs of animals initially exposed to 6 days of 0.4 or greater than 0.95 FiO2. The dose dependency of oxygen-induced lung injury is complex. Straightforward, stepwise dose-response adequately describes the evolution of microscopic injury and slowing of alveolar development in hyperoxia, but the dose dependency is not as clearly identified in the oxygen-induced retardation of lung growth including DNA content and in changes in antioxidant enzyme activities. Changes in lung compliance clearly do not follow expected dose response relationships.
 ...
PMID:The development of the newborn rat lung in hyperoxia: a dose-response study of lung growth, maturation, and changes in antioxidant enzyme activities. 725 58

Isoxsuprine, a beta-sympathomimetic agent used clinically to delay premature parturition and to possibly accelerate fetal lung maturation, was administered to pregnant rats at 48 and 24 h prior to delivery. Newborn rats were placed in 96-98% O2 (or room air) to determine if the prenatal isoxsuprine treatment compromised their tolerance to prolonged hyperoxic exposure. (Exogenous catecholamines are known to exacerbate O2 toxicity in adult animals). Survival of the isoxsuprine-treated pups in O2 (52%) was no different than for control neonates exposed to hyperoxia for 7 days (57%) (P = 0.22). Body weight, lung weight, lung protein, and DNA content of the newborns were also not altered by the prenatal isoxsuprine treatment. Lung antioxidant enzyme activities for superoxide dismutase, catalase, and glutathione peroxidase were the same at birth in the isoxsuprine-treated and control rat pups, and the enzyme activities increased in response to hyperoxic exposure in each group to an equivalent degree. Thus, in utero treatment with isoxsuprine had no apparent adverse effect on newborn rats exposed to a prolonged O2 challenge.
 ...
PMID:Effect of prenatal isoxsuprine on pulmonary oxygen toxicity in the newborn rat. 737 21

Surfactant liposomes, encapsulating CuZn-superoxide dismutase (SOD) and catalase, increase alveolar type II cell antioxidant activity and protect cells against oxidant stress. We examined whether intratracheal instillation of antioxidant-surfactant liposomes increases lung antioxidant activity in premature rabbits. Pregnant New Zealand White rabbits were delivered by cesarean section on day 28 or 29 of gestation or allowed to deliver spontaneously. After premature birth or at 2 days of age in the term rabbits, the pups from each litter were divided into four groups. One group received 0.1 ml/15 g birth wt of antioxidant-surfactant liposomes by intratracheal injection and was then exposed to hyperoxia (> 95% oxygen) for 24 h and killed. The second group received an equal amount of surfactant liposomes without antioxidant enzymes and was exposed to hyperoxia for 24 h. The third group received air placebo and was exposed to hyperoxia for 24 h, and the fourth group was killed after birth if premature or at 2 days of age if term. After the pups were killed, lung homogenates were investigated for total SOD and catalase activity and DNA content. Each treatment group consisted of 12-15 rabbit pups. Lung antioxidant enzyme activity increased with advancing maturity. Among the premature rabbits, total lung SOD and catalase activity were lowest in the pups killed before hyperoxia and the air placebo controls exposed to hyperoxia, intermediate in the pups treated with liposomes without antioxidant enzymes and hyperoxia, and highest in the pups that received antioxidant-surfactant liposomes and hyperoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Antioxidant-surfactant liposomes mitigate hyperoxic lung injury in premature rabbits. 749 79

Hyperoxia causes a reproducible pattern of lung injury and repair in rodents, in which proliferation of alveolar epithelial cells (AEC) and fibroblasts is observed during recovery. We postulated that if quiescent cells are stimulated to reenter the cell cycle, then cyclin expression and cyclin-dependent protein kinase activity would be reactivated in AEC during the repair process after hyperoxic lung injury. To test this hypothesis, we exposed adult rats to short-term hyperoxia, followed by recovery for various times in room air. Cellular proliferation in vivo was confirmed by 1) flow cytometric analysis of DNA content (FACS) of freshly isolated AEC and 2) immunohistochemistry of proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine (BrdU) incorporation into DNA on lung sections. The percentage of freshly isolated AEC in S phase and G2/M phase on FACS analysis increased twofold to a maximum of 16.5%, after 48 h in 100% oxygen and 48 h recovery in air. Cyclins A and D and p34cdc2 protein expression were also increased during the recovery period; while p33cdk2 and p34cdk4 increased only slightly. p34cdc2 histone H1 kinase activity, both in whole lung and in AEC, decreased initially after 48 h in oxygen. However, a marked increase in p34cdc2 kinase activity was observed at 48 h recovery in whole lung and returned to baseline by 72 h. In isolated and cultured AEC, p34cdc2 kinase activity was maximal at 24 h of recovery in air. We conclude that cyclins A and D and p34cdc2 protein expression and p34cdc2 kinase activity are increased in vivo during recovery from hyperoxic lung injury in both adult rat lungs and in AEC isolated from these lungs. We speculate that the induction of cyclin-dependent protein kinase activity is a key event in mediating the proliferative cellular repair response to lung injury.
 ...
PMID:Induction of A- and D-type cyclins and cdc2 kinase activity during recovery from short-term hyperoxic lung injury. 753 63

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.
 ...
PMID:Molecular responses to hyperoxia in vivo: relationship to increased tolerance in aged rats. 759 40

Oxidative damage to the cell has been implicated in the pathogenesis of a number of disorders, including chronic inflammation, aging, and cancer. Manganese superoxide dismutase (Mn-SOD) plays a major role in the protection of the mitochondrion from oxidative damage due to superoxide radicals and other excited oxygen species. In this report we describe the genomic organization and DNA sequence of the murine MnSOD gene. This gene is interrupted by four introns. The coding sequence of this gene was examined in C57BL/6J and C3H/HeJ mice that are SUSCEPTIBLE AND RESISTANT, respectively, to the pulmonary injuries induced by the inhaled oxidants, ozone, and hyperoxia. Since the predicted amino acid sequence for MnSOD does not differ for these strains, nor does the size or steady-state level of this transcript, biologic variability in the pulmonary inflammatory response to ozone and hyperoxia does not arise from an altered gene structure. Examination of the noncoding sequence revealed a dC.dA polymorphism in intron 2 and a StyI RFLV in intron 4 of the MnSOD gene. These sequence and mapping data provide the basis for continued study of biologic variability in the MnSOD gene as a cause of disease.
 ...
PMID:Structure and DNA sequence of the mouse MnSOD gene. 761 35

Mild oxidative stress as exerted by culture of human WI-38 fibroblasts under 40% oxygen partial pressure blocks proliferation irreversibly after one to three population doublings. Hyperoxically blocked cells are similar to senescent ones in terms of general morphology and lipofuscin accumulation. Moreover, they, like senescent fibroblasts, are blocked preferentially in G1 as evident from DNA content measurements by flow cytometry. Southern blotting of AluI- and HinfI-restricted genomic DNA shows an increase of the rate of telomere shortening from 90 bp per population doubling under normoxia to more than 500 bp per population doubling under hyperoxia. In every case, proliferation is blocked if a telomere cutoff length of about 4 kb is arrived at. The fact that telomere length correlates with the final inhibition of proliferation under conditions of varied oxidative stress, while the population doubling level does not, suggests that telomere shortening provides the signal for cell cycle exit in senescence. In postmitotic cells, no further telomere shortening occurs. However, the sensitivity of terminal restriction fragments to S1 nuclease increases, indicating the accumulation of single-strand breaks in telomeres of nondividing fibroblasts. This effect is found both under normoxic and hyperoxic culture, although it is more pronounced under conditions of higher oxidative stress. It might be speculated that accumulation of single-strand breaks and the resultant loss of distal single-stranded fragments during replication could be a major cause of telomere shortening, possibly more important than incomplete replication per se.
 ...
PMID:Mild hyperoxia shortens telomeres and inhibits proliferation of fibroblasts: a model for senescence? 766 35

The HAP1 protein (also known as APE/Ref-1) is a bifunctional human nuclear enzyme required for repair of apurinic/apyrimidinic sites in DNA and reactivation of oxidized proto-oncogene products. To gain insight into the biological roles of HAP1, the effect of expressing antisense HAP1 RNA in HeLa cells was determined. The constructs for antisense RNA expression consisted of either a full-length HAP1 cDNA or a genomic DNA fragment cloned downstream of the CMV promoter in pcDNAneo. Stable HeLa cell transfectants expressing HAP1 antisense RNA were found to express greatly reduced levels of the HAP1 protein compared to equivalent sense orientation and vector-only control transfectants. The antisense HAP1 transfectants exhibited a normal growth rate, cell morphology and plating efficiency, but were hypersensitive to killing by a wide range of DNA damaging agents, including methyl methanesulphonate, hydrogen peroxide, menadione, and paraquat. However, survival after UV irradiation was unchanged. The antisense transfectants were strikingly sensitive to changes in oxygen tension, exhibiting increased killing compared to controls following exposure to both hypoxia (1% oxygen) and hyperoxia (100% oxygen). Consistent with a requirement for HAP1 in protection against hypoxic stress, expression of the HAP1 protein was found to be induced in a time-dependent manner in human cells during growth under 1% oxygen. The possible involvement of a depletion of cellular glutathione being linked to the hypoxic stress-sensitive phenotype of the antisense HAP1 transfectants came from the finding that they also exhibited hypersensitivity to buthionine sulphoximine, an inhibitor of glutathione biosynthesis. We conclude that the HAP1 protein is a key factor in cellular protection against a wide variety of cellular stresses, including DNA damage and a change in oxygen tension.
 ...
PMID:A role for the human DNA repair enzyme HAP1 in cellular protection against DNA damaging agents and hypoxic stress. 780 Apr 76

Otitis media represents a continuum of inflammatory stages frequently in association with bacteria and/or endotoxin. Furthermore, the disease is often treated with insertion of ventilation tubes, which causes hyperoxia relative to the physiological state in the tympanic cavity. The present study was undertaken to quantitate the interaction between endotoxin and relative hyperoxia in cultures of rabbit middle ear fibroblasts incubated in normal middle ear gas and atmospheric air, respectively. Growth was monitored by determination of DNA, cell protein and cell division. The synthetic activity was estimated by collagen production. The antioxidant defense was determined by measuring the intra-and extracellular concentrations of superoxide dismutase (SOD). The results demonstrated that hyperoxia significantly impaired the growth of middle ear fibroblasts, which was compensated for by addition of endotoxin stimulating the growth. The collagen synthesis increased significantly in atmospheric air with a synergistic effect of endotoxin. Hyperoxia induced intracellular SOD formation, while endotoxin tended to reduce the synthesis. Finally, exposure to atmospheric air caused significantly larger amounts of reducing agents extracellularly in cultures without endotoxin compared to endotoxin incubated cultures. It is suggested that endotoxin possess both synergistic and antagonistic potential as regards the effects of relative hyperoxia, and that the interaction between endotoxin and hyperoxia may be an important factor in otitis media.
 ...
PMID:The influence of endotoxin upon middle ear fibroblasts cultured in normal middle ear gas and atmospheric air. 782 3

Glutathione reductase (GR) protects tissues from oxidant injury by catalysing the reduction of glutathione disulfide (GSSG) to glutathione (GSH). In order to study the effect of GR in protecting cells from oxidant injury, we generated Chinese hamster ovary (CHO) cell lines stably transformed after antisense-oriented gene transfection. The coding region of the human GR was cloned using revere transcription PCR method and selected by transient expression study in mammalian cells. A clone HGR135 showed overexpression of GR in CHO cells and was proved to have no base substitution. This clone, then, was ligated into MEP4 expression vector in an antisense orientation to the human metallothionein promoter and transfected to CHO cells with polybrene. Among 12 cell lines isolated, G17 showed to have the least GR activity (48% of the control), while another four were mildly GR deficient. Southern hybridization of genomic DNA digests and transformation experiment on E. coli revealed that the promoter-antisense coding region component was integrated. Northern hybridization detected reduced amount of GR transcript but no antisense message. Baseline cellular GSH concentrations were lower in G17 than in control (25.7 +/- 2.5 vs. 36.1 +/- 1.9 nmole/mg protein, P < 0.05), while cellular GSSG concentrations were higher (0.61 +/- 0.19 vs. 0.39 +/- 0.09 nmole/mg protein, P < 0.05). After four hours of treatment of G17 and control cells with increasing doses (1 to 10 mM) of t-butylhydroperoxide (t-BuOOH), cellular GSH concentrations in G17 decreased with an elevation of GSSG concentration at 1 mM followed by no further increase at higher t-BuOOH concentration, while GSSG concentrations increased in the control cells without reduction of GSH concentrations at 1-5 mM t-BuOOH treatment. The concentrations of GSH were lower in G17 than in controls at all doses of t-BuOOH. Four hours of exposure to 10 mM t-BuOOH resulted in greater LDH release in G17 than in control (57.3 +/- 4.7 vs. 32.1 +/- 6.5%, P < 0.05). Similarly, G17 cells released more of their LDH to the media than did CHO cells in response to exposure to 95% O2 for 72 hours (19.3 +/- 5.9 vs. 11.9 +/- 5.4%, P < 0.05). The partial GR deficiency in G17 cells impairs their ability to recycle GSSG and this deficiency offers the best explanation for the increased sensitivity of these cells to injury by t-BuOOH or hyperoxia.
 ...
PMID:[Establishment of Chinese hamster ovary cell lines with reduced expression of glutathione reductase after antisense-oriented gene transfection and assessment of the sensitivity to oxidant injury]. 786 64


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>