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)

Antioxidant enzymes, including superoxide dismutase, are important for protecting the lung against O2 injury. Manganese superoxide dismutase (Mn-SOD) is a superoxide anion (O2-.) scavenger located in the mitochondria, a primary site of O2-. production during hyperoxia. We studied the effects of tumor necrosis factor (TNF-alpha), a macrophage-derived cytokine, on Mn-SOD expression in human pulmonary adenocarcinoma cells. TNF-alpha significantly increased Mn-SOD activity and mRNA in a dose-and time-dependent manner. Mn-SOD activity was increased 3-fold and mRNA 20-fold after a 48-h incubation with TNF-alpha (25 ng/ml). To examine the mechanism of this increase, cells were incubated for 48 h with TNF-alpha (25 ng/ml) with or without cycloheximide (10 microns) or actinomycin D (10 micrograms/ml). Actinomycin D blocked the induction of Mn-SOD mRNA by TNF-alpha, but cycloheximide did not. These findings suggest that the effect of TNF-alpha requires gene transcription but not synthesis of new protein intermediates. To test the hypothesis that increased Mn-SOD protects against oxidative injury, pulmonary adenocarcinoma cells were incubated in TNF-alpha (25 ng/ml) for 48 h and then exposed to paraquat (PQ+), an intracellular O2-. generator. Cells pretreated with TNF-alpha had significantly improved survival in PQ+ compared with controls. At the LD50 (6 microns) for control cells, 95% of TNF-alpha-treated cells survived, 85% at the LD75 (10 microns), and 77% at the LD90 (14 microns). Our results suggest that the induction of Mn-SOD by TNF-alpha in pulmonary adenocarcinoma cells is pretranslationally mediated and that increasing Mn-SOD activity with TNF-alpha confers protection against O2 radicals.
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PMID:Tumor necrosis factor-alpha increases Mn-SOD expression: protection against oxidant injury. 185 Feb 7

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.
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PMID:Structure and DNA sequence of the mouse MnSOD gene. 761 35

Aerobic metabolism requires a continuous oxygen supply, which in turn can form partially reduced species (free radicals) that damage cellular components. To prevent this, organisms have elaborate free radical-scavenging defenses that include the superoxide dismutases. The lungs are unique in their role as an oxygen-gathering system, making these defenses critical to lung integrity. Manganese superoxide dismutase (Mn-SOD) levels increase in rats exposed to sublethal doses of hyperoxia and correlate with the development of tolerance to higher levels of hyperoxia. Although pulmonary Mn-SOD protein and mRNA levels both change with hyperoxia, the timing and levels differ dramatically. Lung heterogeneity makes extrapolation of data from whole tissue homogenates or cultures difficult. In this study, in situ hybridization of Mn-SOD in the lungs of adult rats exposed to air or to 85% O2 for 3 days was performed. In animals exposed to either air or 85% O2, Mn-SOD transcripts were present in arterioles, the septal tips of alveolar ducts, alveolar type II cells, and mesothelial cells. Hyperoxic lung had an intense, continuous labeling of the pleura that was distinctly greater than the intermittent labeling of the pleura found in control animals. The high level of expression of Mn-SOD mRNA in alveolar duct septal tips in both control and O2-exposed animals may be secondary to increased aerobic activity in these regions, which contain collagen and elastin and are important stress-bearing elements in the lung. Alveolar type II cells are metabolically active secretory cells and thus may experience increased endogenously generated oxidative stress. Pleural effusions are common after hyperoxic exposures, suggesting damage to the mesothelium.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Distribution of manganese superoxide dismutase mRNA in normal and hyperoxic rat lung. 848 Dec 34

Manganese superoxide dismutase (MnSOD) activity falls approximately 50% in lung during 48 h of exposure of adult rats to > 95% O2 (L. B. Clerch and D. Massaro. J. Clin. Invest. 91: 499-508, 1993). We now show that hyperoxia also decreased MnSOD activity in lungs of adult baboons, making the phenomenon potentially more important to humans. In rats, a decrease in lung MnSOD activity during an initial 48 h of exposure to > 95% O2 and its increase during an immediately subsequent 24 h in air were due to decreases and increases, respectively, in MnSOD specific activity and synthesis rate; the latter was due to altered translational efficiency. The concentration in the lung of copper-zinc superoxide dismutase mRNA, catalase mRNA, and glutathione peroxidase mRNA, unchanged during the initial 48 h of exposure to O2, rose approximately twofold during reexposure to O2 after 24 h in air. The demonstration that the fall in MnSOD activity is translationally and posttranslationally regulated during the initial exposure to hyperoxia suggests that gene transfer to increase MnSOD activity in hyperoxic lungs may also require therapy that maintains translational efficiency and MnSOD specific activity.
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PMID:Molecular mechanisms of antioxidant enzyme expression in lung during exposure to and recovery from hyperoxia. 953 Jan 65

Lipopolysaccharide (LPS) treatment increases survival of rats, but not of mice, during hyperoxia. Manganese superoxide dismutase (Mn SOD) in the lung plays a critical role in LPS-induced tolerance to hyperoxia in rats. Therefore, we now compared the response of lung Mn SOD with treatment of mice and rats with LPS. LPS treatment of rats increased Mn SOD activity and protein concentration, did not change its specific activity, increased Mn SOD mRNA concentration 35-fold, and elevated Mn SOD synthesis 50% without changing general protein synthesis. LPS treatment of mice did not alter any of these parameters except for a 16-fold increase in Mn SOD mRNA concentration. Mn SOD translational efficiency (synthesis/mRNA concentration) was diminished 93% in rat lung and 76% in mouse lung by treatment with LPS. However, the absolute translational efficiency was twofold higher in lungs of LPS-treated rats than in lungs of LPS-treated mice. The failure of LPS to raise Mn SOD activity in mouse lungs is due, at least in part, to a smaller increase in Mn SOD mRNA and lower translational efficiency in LPS-treated mice than in LPS-treated rats.
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PMID:Regulation of lung manganese superoxide dismutase: species variation in response to lipopolysaccharide. 1033 25

Oxygen toxicity is believed to arise from changes in the rates at which cells generate reactive oxygen species (ROS). Sensitivity to hyperoxia has been postulated to depend on levels of antioxidant defense. Human cells obtained from fetal tissues have lower antioxidant defenses than those obtained from adult tissue. The present study was performed to determine whether the differences in fetal and adult antioxidant defense levels modulated their responses to changes in the ambient oxygen concentration. Our results demonstrate that oxygen modulates the proliferation of human fetal and adult skin fibroblasts in a similar fashion. In general, skin fibroblasts grew better at approximately 31 mm Hg, regardless of donor age. Manganese superoxide dismutase, catalase, and glutathione peroxidase activities were lower in fetal cells than in adult fibroblasts. Copper/zinc superoxide dismutase and glucose-6-phosphate dehydrogenase were similar in fetal and postnatal tissues and were unaltered appreciably by hyperoxic exposure. Glutathione concentration increased at higher oxygen tensions; however, the increase was much greater in fetal cells than in cultures derived from adult skin. These observations demonstrate that the capacity of fetal and adult cells to cope with oxidative stress, while similar, result from distinct mechanisms.
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PMID:Effects of ambient oxygen concentration on the growth and antioxidant defenses of of human cell cultures established from fetal and postnatal skin. 1182 51