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)

Treatment of cells or organisms with agents that increase the expression of MnSOD confers resistance to certain types of oxidative damage. However, since these treatments also affect other cellular systems with antioxidant capabilities, the role of MnSOD remains uncertain. To better determine whether increased MnSOD expression confers increased resistance to oxidant stress, a eukaryotic expression vector harboring a mouse MnSOD cDNA was constructed. Bovine lung microvessel endothelial cells were co-transfected with the MnSOD expression vector and pSV2-neo, which contains the neor gene and provides a dominant selectable marker. Control clones were generated by transfecting the cells with psV2-neo alone. Stably transfected cell lines were selected and cell lines overexpressing MnSOD were confirmed by Northern blotting, immunoblot analysis, and activity gels. The activities of copper/zinc superoxide dismutase, catalase, and glutathione peroxidase were examined, and no increase in activity of any of these enzymes was detected. Cells were exposed to hyperoxic challenge by treatment with 95% O2 and 5% CO2 for 24 h. Viability was assessed by a clonogenic assay. The cell lines that overexpressed MnSOD showed a twofold increase in survival compared to control cells. These results demonstrate a significant resistance to hyperoxia induced oxidative stress in endothelial cells overexpressing MnSOD.
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PMID:Overexpression of manganous superoxide dismutase (MnSOD) in pulmonary endothelial cells confers resistance to hyperoxia. 796 7

In evaluating the relative expression of copper-zinc and manganese superoxide dismutase (CuZnSOD and MnSOD) in vivo in states like Down syndrome in which one dismutase is present at increased levels, we measured activities of both enzymes, in tissues of control and transgenic mice constitutively expressing increased levels of CuZnSOD, during exposure to normal and elevated oxygen tensions. Using SOD gel electrophoresis assay, CuZnSOD and MnSOD activities of brain, lung, heart, kidney, and liver from mice exposed to either normal (21%) or elevated (> 99% oxygen, 630 torr) oxygen tensions for 120 h were compared. Whereas CuZnSOD activity was elevated in tissues of transgenic relative to control mice under both normoxic or hyperoxic conditions, MnSOD activities in organs of transgenic mice were remarkably similar to those of controls under both conditions. To confirm the accuracy of this method in quantitating MnSOD relative to CuZnSOD expression, two other methods were utilized. In lung, which is the organ exposed to the highest oxygen tension during ambient hyperoxia, a sensitive, specific ELISA for MnSOD was used. Again, MnSOD protein was not different in transgenic relative to control mice during exposure to air or hyperoxia. In addition, lung MnSOD protein was not changed significantly by exposure to hyperoxia in either group. In kidney, a mitochondrion-rich organ, SOD assay, before and after inactivation of CuZnSOD with diethyldithiocarbamate, was used. MnSOD activity was not different in organs from air-exposed transgenic relative to control mice. The data indicated that expression of MnSOD in vivo was not affected by overexpression of the CuZnSOD and, therefore, the two enzymes are probably regulated independently.
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PMID:Expression of manganese superoxide dismutase is not altered in transgenic mice with elevated level of copper-zinc superoxide dismutase. 813 89

Exposure of rats to hyperoxia or to treatment with endotoxin, increases lung manganese superoxide dismutase (MnSOD) gene expression. However, the paths by which these environmental signals are transduced into enhanced MnSOD gene expression are unknown. We now provide evidence that heterotrimeric G proteins are involved in the hyperoxia-induced increase in lung MnSOD gene expression but that pertussis toxin-sensitive G proteins are not involved in the endotoxin-induced elevation of lung MnSOD gene expression. We also show that treating rats with pertussis toxin decreased lung MnSOD activity approximately 50%. This decline in MnSOD activity occurred without a change in the lung activity of copper-zinc SOD, catalase, or glutathione peroxidase. In air-breathing rats, the pertussis toxin-induced decrease in MnSOD activity was associated with the development of lung edema, pleural effusion with a high concentration of protein, and biochemical evidence of lung oxygen toxicity. Compared to air-breathing rats, maintenance of pertussis toxin-treated rats under hypoxic or hyperoxic conditions respectively decreased or increased intrathoracic fluid. Endotoxin treatment elevated lung MnSOD activity and protected pertussis toxin-treated rats from an increase in intrathoracic fluid.
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PMID:Pertussis toxin treatment alters manganese superoxide dismutase activity in lung. Evidence for lung oxygen toxicity in air-breathing rats. 820 Sep 62

Dexamethasone (10 mg/kg/day) or vehicle was administered in a randomized, controlled fashion to 3-day preterm guinea pigs exposed to either 21% oxygen or 95% oxygen for 72 hr and maintained in room air for a further 96 hr. Treatment with dexamethasone had no effect on survival of preterm pups maintained in either 21% or 95% O2. Dexamethasone treatment reduced the growth rate of pups, the effect occurring earlier (0-3 days) in 21% O2-treated pups than in 95% O2-treated pups (5-7 days). Exposure to 95% O2 reduced the survival rate of preterm animals (73% vs 100%, P < 0.05). Surviving pups developed acute lung injury, characterized by the accumulation of a protein-rich exudate in the alveoli and an infiltration of inflammatory cells, particularly neutrophils into the lung. Dexamethasone treatment attenuated the pulmonary inflammatory cell infiltration, in particular neutrophils, both during oxygen exposure (16.4 x 10(4) vs 9.4 x 10(4)/mL; P < 0.05) and following return to ambient conditions (28.0 x 10(4) vs 5.1 x 10(4)/mL; P < 0.05). Elastase activity in bronchoalveolar lavage fluid, which was primarily of neutrophil origin, was unchanged by dexamethasone treatment. Dexamethasone-treated pups had increased pulmonary antioxidant enzyme activities (Cu/Zn-superoxide dismutase; Mn-superoxide dismutase, catalase and glutathione peroxidase) during recovery from oxidative injury. Although there was both a marked reduction in numbers of neutrophils in the lung and elevated pulmonary antioxidant enzyme activities in dexamethasone-treated pups, the degree of microvascular permeability, as determined by both the lung wet weight/dry weight ratio and the presence of plasma proteins in the lavage fluid, was unchanged. Combined, these results imply that dexamethasone, although capable of blunting the influx of neutrophils to the hyperoxia-exposed lung and inducing antioxidant defences in the immature lung, cannot modify the progression of acute oxygen-induced injury of the immature lung.
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PMID:Dexamethasone treatment fails to reduce oxygen-induced lung injury in the preterm guinea pig. Effects on pulmonary inflammation and antioxidant status. 824 Apr 12

We examined the effects of inhibition of Cu,Zn superoxide dismutase (Cu,Zn SOD) and catalase (Cat) activities on the steady-state mRNA levels of the three major antioxidant enzymes [Cu,Zn SOD, Cat, and glutathione peroxidase (GP)] in human umbilical vein endothelial cells under normoxia and hyperoxia. Inhibition of Cat activity by aminotriazole was not associated with alteration of the other antioxidant enzymes or with potentiation of cell injury. On the other hand, inhibition of Cu,Zn SOD activity by N-N'-diethyl-dithiocarbamate (DDC) was associated with an increase in Cu,Zn SOD mRNA level and a decrease in Cat and GP mRNA level. The combination of DDC and hyperoxia treatments was associated with an additive effect on Cu,Zn SOD message. We propose that these coordinate mRNA changes might be an adaptation to the oxidative environment. This proposal supports the concept that the intracellular O2 metabolites themselves could be the signals that trigger the antioxidant enzymes gene expression.
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PMID:Effects of inhibition of catalase and superoxide dismutase activity on antioxidant enzyme mRNA levels. 827 80

The time course and nature of the pulmonary inflammatory and antioxidant responses, both during and after hyperoxic-induced acute lung injury were studied in the preterm guinea pig. Three-day preterm (65 days gestation) guinea pigs were randomly exposed to either 21% O2 (control) or 95% O2 (hyperoxia) for 72 hours. All pups were then maintained in ambient conditions for up to a further 11 days, during which time lung damage was monitored. In animals exposed to hyperoxia, evidence of acute lung injury and inflammation was characterized by a marked increase in microvascular permeability and elevated numbers of neutrophils in bronchoalveolar lavage fluid. Protein concentration, elastase-like activity and elastase-inhibitory capacity in lavage fluid were at a maximum at the end of the 72 hours hyperoxic exposure. Four days later, all values had returned to control levels. In contrast, increased numbers of neutrophils, macrophages and lymphocytes were recovered in the lavage fluid during this early recovery period. Coinciding with the influx of inflammatory cells, there was a significant increase in glutathione peroxidase, manganese superoxide dismutase and catalase activities in immature lung. Lung copper/zinc superoxide dismutase activity remained unchanged during both experimental periods. The strong temporal relationship between the influx of inflammatory cells to the lung and the induction of pulmonary antioxidant enzyme defences suggests that a common mechanism underlies both responses. These findings have led us to regard inflammation in the hyperoxic-injured immature lung as a beneficial event and not, as previously suggested, as part of the injurious process.
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PMID:Temporal association between pulmonary inflammation and antioxidant induction following hyperoxic exposure of the preterm guinea pig. 837 May 48

Reactive oxygen species have been postulated to be a causal factor in the aging process due to their ability to inflict molecular damage. The role of the enzyme copper-zinc superoxide dismutase (Cu-Zn SOD; superoxide:superoxide oxidoreductase; EC 1.15.1.1), which scavenges superoxide anion radicals, as a longevity determinant was examined in transgenic Drosophila melanogaster. A genomic fragment containing the Drosophila Cu-Zn SOD gene was introduced into the germ cells via a P element containing Casper vector. In different transgenic lines, overexpression of SOD by 32-42% above normal had either a minor and/or an insignificant effect on life span of the flies and their ability to withstand experimental oxidative stress, induced by paraquat intake and exposure to hyperoxia (100% oxygen). Transgenics showing a small increase in mean life span also exhibited a corresponding improvement in their resistance to hyperoxia but not paraquat. The maximum life span of populations was not affected.
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PMID:Effects of Cu-Zn superoxide dismutase overexpression of life span and resistance to oxidative stress in transgenic Drosophila melanogaster. 844 64

The 27-day-old rat exposed to 100% oxygen (O2) for 8 days will have predictable lung vascular and parenchymal changes at 60 days of age. Using this model, the goals of this study are (1) to measure the lung antioxidant enzyme activities serially following intratracheal PEG antioxidant therapy during the 8-day O2 exposure; and (2) to assess chronic cardiopulmonary changes in the O2-exposed rats treated with PEG-CAT and/or PEG-CuZn SOD given intraperitoneally (IP) and/or intratracheally (IT). The study encompassed 202 male rats exposed to room air or oxygen. CuZn SOD doses were 300 U IT and 2000 U IP. The CAT dose was 500 or 4000 U IT and 10,000 U IP. At 60 days of age, the right ventricular systolic pressure (RVP), RV weight, % acinar wall arterial thickness, and parenchymal air space were significantly increased in O2-exposed rats compared to RA rats. The RVP, RV weight, and parenchymal changes were prevented by daily IT PEG-CAT 4000 U + CuZn SOD 300 U but the increased small artery muscularization was not. Three hours after the initial dose of IT PEG-CAT 4000 U, lung CAT activity was more than doubled and remained constant throughout the 8-day daily treatment course. This dose of CAT depressed the induction response to O2 of CuZn and MnSOD. It is concluded that daily intratracheal administration of PEG-CAT 4000 U + CuZn SOD 300 U can significantly ameliorate some of the chronic parenchymal and vascular lung O2 toxic changes. However, it appears that high-dose exogenous PEG-CAT suppresses the endogenous enzyme induction to hyperoxia of both CuZn and Mn-SOD.
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PMID:Lung antioxidant enzymes and cardiopulmonary responses in young rats exposed to hyperoxia and treated intratracheally with PEG catalase and superoxide dismutase. 846 59

We have investigated the relationship between intracellular glutathione levels and the inducibility of the mRNAs encoding the major antioxidant enzymes Cu,Zn superoxide dismutase (Cu,Zn SOD), catalase (CAT), glutathione peroxidase (GP), and the stress protein heme oxygenase (HO) following exposure of human umbilical vein endothelial cells (HUVEC) to either hypoxanthine-xanthine oxidase or 95% O2. Treatment of HUVEC with 2 and 200 microM buthionine sulfoximine (BSO) for 16 h reduced total glutathione (GSH) levels by 51 and 95%, respectively, whereas treatment with 100 microM diethylmaleate (DEM) for 24 h increased the cellular GSH content by 58%. None of these treatments affected the responsiveness of HUVEC to a subsequent oxidant challenge, in terms of antioxidant enzymes activities and mRNA levels. On the contrary, HO mRNA was significantly induced by both BSO and DEM, as well as by hyperoxia, albeit to a different extent. We conclude that intracellular redox changes do not appear to regulate the expression of the mRNAs encoding Cu,Zn SOD, CAT, and GP. Furthermore, factors other than endogenous thiols may play a role in the control of HO mRNA expression.
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PMID:Variable glutathione levels and expression of antioxidant enzymes in human endothelial cells. 849 25

Effects of prolonged action of low-pressure oxygen (0.3 MPa, 5h) on the free-radical oxidation (FRO) intensity were investigated just after oxygen exposure and 1, 3, 7, days after that. The FRO increase against the background of the anti-radical systems depression was shown by means of blood plasma chemiluminescent analysis. Under these conditions SOD activity and the content of diene conjugates and Schiff's bases increase in erythrocyte membranes. The displacement of equilibrium between pro- and antioxidants and antioxidants contents towards the latter took place in blood plasma on the 1st day after oxygen exposure. The erythrocyte SOD activity was raised while catalase activity was diminished. The last one was accompanied with the decrease in erythrocyte membrane diene conjugates amount. The secondary blood plasma and erythrocyte membrane FRO elevation was observed on the 3rd day after the exposure and, it was held on the 7th day after hyperoxia. The FRO increase in post-hyperoxia period was established.
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PMID:[Free radical processes in the rat blood during hyperbaric oxygenation and in the posthyperoxic period]. 875 11


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