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

The content of glutamic, asparaginic and gamma-aminobutyric (GABA) acids in norm and under hyperoxia was determined in different cerebral areas of susliks living in places at different heights above sea level. In susliks at a height of 1700-2000 m above sea level the content of glutamate aspartate and GABA lowers significantly as compared to that in susliks at a height of 500-600 m above sea level. Under the effect of oxygen 6 at. ga at the 22nd minute on the average there occur convulsions in susliks living both in high mountains and middle mountains. Acute oxygen poisoning is not accompanied by noticeable shifts in the content of free dicarboxylic amino acids in the studied cerebral areas of middle-mountain susliks and is characterized only by an increase of the GABA content in the cerebellum. In high-mountain susliks the content of glutamate under these conditions increases in great cerebral hemispheres, while the asparate content lowers in cerebral hemispheres and cerebellum. In the latter the drop in the content of GABA is statistically significant.
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PMID:[Content of dicarboxylic acids and GABA in normal suslik brain and under the effect of oxygen at higher pressure]. 55 58

The content of homocarnosine, GAMA, histidine, glutaminic acid and activity of glutamate decarboxylase were studied in four regions of rats brain: cerebral hemispheres, midbrain, diencephalon and cerebellum, in norm and under hyperoxia. A considerable decrease in the content of homocarnosine, GAMA and histidine is observed in all the studied regions of the rat brain in the convulsion stage of oxygen poisoning. A decrease in the glutamate decarboxylase activity is the reason for a drop in the GAMA content. Homocarnosine in the brain is bound functionally with the GAMA level.
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PMID:[Metabolism of homocarnosine and gamma-amino butyric acid in different regions of rat brain under hyperoxia]. 72 92

Previous work has shown that irrespective of the route of exposure methyl isocyanate (MIC) caused acute lactic acidosis in rats (Jeevaratnam et al., Arch. Environ. Contam. Toxicol. 19, 314-319, 1990) and the hypoxia was of stagnant type due to tissue hypoperfusion resulting from hypovolemic hypotension in rabbits administered MIC subcutaneously (Jeevarathinam et al., Toxicology 51, 223-240, 1988). The present study was designed to investigate whether MIC could induce histotoxic hyperoxia through its effects on mitochondrial respiration. Male Wistar rats were used for liver mitochondrial and submitochondrial particle (SMP) preparation. Addition of MIC to tightly coupled mitochondria in vitro resulted in stimulation of state 4 respiration, abolition of respiratory control, decrease in ADP/O ratio, and inhibition of state 3 oxidation. The oxidation of NAD(+)-linked substrates (glutamate + malate) was more sensitive (five- to sixfold) to the inhibitory action of MIC than succinate while cytochrome oxidase remained unaffected. MIC induced twofold delay in the onset of anerobiosis, and cytochrome b reduction in SMP with NADH in vitro confirms inhibition of electron transport at complex I region. MIC also stimulated the ATPase activity in tightly coupled mitochondria while lipid peroxidation remained unaffected. As its hydrolysis products, methylamine and N,N'-dimethylurea failed to elicit any change in vitro; these effects reveal that MIC per se acts as an inhibitor of electron transport and a weak uncoupler. Administration of MIC sc at lethal dose caused a similar change only with NAD(+)-linked substrates, reflecting impairment of mitochondrial respiration at complex I region and thereby induction of histotoxic hypoxia in vivo.
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PMID:In vitro and in vivo effect of methyl isocyanate on rat liver mitochondrial respiration. 147 Nov 48

Cellular intoxication by elevated concentrations of O2 may be considered as a model for accelerated cellular aging processes resulting from excessive free radical production by normal metabolic pathways. We describe here that exposure of HeLa cell cultures to 80% O2 for 2 days causes progressive growth inhibition and loss of reproductive capacity. This intoxication was correlated with inhibition of cellular O2 consumption and inactivation of 3 mitochondrial flavoproteins, i.e., partial inactivation of NADH and succinate dehydrogenases and total inactivation of alpha-ketoglutarate dehydrogenase. As alpha-ketoglutarate dehydrogenase controls the influx of glutamine/glutamate into the Krebs cycle, which is the major pathway for oxidative ATP generation in HeLa cells, the inactivation of alpha-ketoglutarate dehydrogenase was expectedly correlated with a net fall in glutamine/glutamate utilization. Furthermore, a simultaneous increase in glucose consumption and lactate production was observed, indicating that the cellular response to respiratory failure is to generate more ATP from glycolysis. In spite of this response, extensive depletion of ATP was observed. Thus, hyperoxia-induced growth inhibition and loss of clonogenicity seem to be due primarily to an impairment of mitochondrial energy metabolism resulting from inactivation of SH-group-containing flavoprotein enzymes localized at or near the inner mitochondrial membrane. These observations may be relevant for theories implicating loss of mitochondrial function as a prime factor in the aging process.
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PMID:Hyperoxia-induced clonogenic killing of HeLa cells associated with respiratory failure and selective inactivation of Krebs cycle enzymes. 223 21

Continuous exposure of Chinese hamster ovary (CHO) cells to an atmosphere of 98% O2, 2% CO2 (normobaric hyperoxia) leads within a period of several days to cytostasis and clonogenic cell death. Here we report respiratory failure as an important early symptom of oxygen intoxication in CHO cells, resulting in a more than 80% inhibition of oxygen consumption within 3 days of hyperoxic exposure. This inhibition appeared to be correlated with selective inactivation of three mitochondrial key enzymes, NADH dehydrogenase, succinate dehydrogenase, and alpha-ketoglutarate dehydrogenase. The latter enzyme controls the influx of glutamate into the Krebs cycle and is particularly critical for oxidative ATP generation in most cultured cells, which depends on exogenous glutamine rather than glucose as a carbon source. As expected, the inactivation of alpha-ketoglutarate dehydrogenase was correlated with a fall in cellular glutamine utilization, which became apparent from the first day of hyperoxic exposure. Thereafter, glucose utilization and lactate excretion started to increase, up to 3-fold, indicating a cellular response to respiratory failure aimed at increased ATP generation from glycolysis. However, in spite of this response, the cellular ATP level progressively decreased, up to 2.5-fold. Thus, killing of CHO cells by normobaric hyperoxia seems to be due to a severe disturbance of mitochondrial metabolism eventually leading to a depletion of cellular ATP pools.
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PMID:Respiratory failure and stimulation of glycolysis in Chinese hamster ovary cells exposed to normobaric hyperoxia. 235 58

In addition to its participation in a variety of other biochemical reactions, glutathione (GSH) is a major antioxidant. It is regularly generated intracellularly from its oxidized form by glutathione reductase activity that is coupled with a series of interrelated reactions. Synthesis of GSH also takes place intracellularly by a two-step reaction, the first of which is catalyzed by rate-limiting gamma-glutamylcysteine synthetase activity. Intracellular substrates for GSH are provided both by direct amino acid transport and by a gamma-glutamyl transpeptidase reaction that salvages circulating GSH by coupling the gamma-glutamyl moiety to a suitable amino acid acceptor for transport into the cell. Although the liver is a net synthesizer of circulating GSH, organs such as the kidney salvage GSH through the gamma-glutamyl transpeptidase reaction. Intracellular GSH may be consumed by GSH transferase reactions that conjugate GSH with certain xenobiotics. Elevation of cellular GSH levels in cultured cells in response to hyperoxia or electrophilic agents such as diethylmaleate is coupled with an increase in activity of the Xc- transport system for the amino acids cystine and glutamate. Strategies may be developed for protection against oxidant injury by enhancement of transport systems for precursor amino acids of GSH or by providing substrate that circumvents feedback inhibition of GSH synthesis.
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PMID:Regulation of cellular glutathione. 257 74

Diethyl maleate (DEM, 0.025-0.10 mM) increased glutathione (GSH) levels in calf pulmonary artery endothelial cells up to fivefold in 12-24 h of incubation. Parallel increases occurred in the rates of uptake of cystine and glutamate. The DEM-mediated increases in both GSH levels and glutamate-cystine uptake were inhibited by cycloheximide and actinomycin D, indicating a dependency on protein and RNA synthesis. The stimulatory effects of DEM on amino acid uptake and GSH levels were greater than those in endothelial cells exposed to 80% O2 for 24 h. The effect of hyperoxia on cellular transport processes was also less specific than that of DEM. Although the increase in glutamate uptake produced by hyperoxia appeared to be under the regulation of protein synthesis, the relationship with elevated GSH in the presence of hyperoxia was less clear because of elevation of control cellular GSH by cycloheximide or actinomycin D alone. Inhibition of GSH synthesis by buthionine sulfoximine also stimulated cystine and glutamate uptake. We conclude that elevation of endothelial intracellular GSH by both DEM and hyperoxia is associated with and may be produced by enhanced uptake of precursor amino acids; the effect of DEM is more pronounced and more specific than that of hyperoxia.
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PMID:Increase in endothelial cell glutathione and precursor amino acid uptake by diethyl maleate and hyperoxia. 280 55

We have previously found that exposure of pulmonary artery endothelial cells to hyperoxia or low concentrations of diethyl maleate (DEM) results in elevation of both cellular glutathione (GSH) and uptakes of glutamate and cystine. The present study confirms that this elevation occurs for a variety of lung cells (bovine pulmonary artery endothelial and smooth muscle cells and rat lung fibroblast and epithelial-like cells) but not for human, rat, and chicken erythrocytes. In fact, human and rat erythrocyte GSH levels were reduced substantially at DEM concentrations from 0.05 to 0.5 mM, whereas the GSH level of chicken erythrocytes was almost totally eliminated by 0.05 mM DEM. Also, all erythrocytes failed to accumulate measurable amounts of radioactive glutamate or cystine. The findings suggest the presence of different mechanisms for the regulation of cellular GSH in lung cells from those of erythrocytes. They are consistent with a requirement for a cystine-glutamate transporter and transcriptional and translational events for the elevation of cellular GSH in response to hyperoxia or low levels of DEM in the lung cells.
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PMID:Erythrocytes fail to induce glutathione in response to diethyl maleate or hyperoxia. 280 56

We investigated whether exposure of rats to sublethal hyperoxia (85% O2 for 7 days) raises the levels of proteins antigenically related to Na+ channels in alveolar type II (ATII) cells and, if so, whether this rise was accompanied by an increase in conductive Na+ transport in vitro. ATII cells were isolated from the lungs of these rats at the end of the exposure period. In Western blot studies, a polyclonal antibody raised against Na+ channel protein (NaAb), recognized in a specific manner a 135 +/- 10 kDa polypeptide in plasma membrane vesicles of ATII cells from both control and oxygen-exposed rats. However, higher levels of immunoreactivity were seen in ATII cells from oxygen-exposed rats. When ATII cells were patched in the whole cell mode using symmetrical solutions (150 mM Na(+)-glutamate), outward rectified Na+ currents were observed. When corrected for cell capacitance, both inward and outward currents of ATII cells from rats exposed to hyperoxia were significantly higher than control. Addition of either 1 microM amiloride or 1 microM 5-(N-ethyl-N-isopropyl)-2'-4'-amiloride in the bath solution decreased the magnitude of outward currents of both control and hyperoxic ATII cells by approximately 50%. Taken together, these results indicate that exposure of rats to sublethal hyperoxia results in upregulation of ATII cell conductive pathways with low affinity to amiloride and increased Na+ transport. This may be an early adaptive response that limits the degree of alveolar edema in injured lungs.
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PMID:Upregulation of sodium conductive pathways in alveolar type II cells in sublethal hyperoxia. 830 67

CNS oxygen (O2) toxicity is complex, and the etiology of its most severe manifestation, O2 convulsions, is yet to be determined. A role for depletion of the brain GABA pool has been proposed, although recent data have implicated production of reactive O2 species, e.g. H2O2, in this process. We hypothesized that the production of H2O2 and NH3 produced by monoamine oxidase (MAO) would lead to depletion of GABA and production of nitric oxide (NO.) respectively, and thereby enhance CNS O2 toxicity. In this study, rats treated with an MAO inhibitor (pargyline) or a nitric oxide synthase inhibitor (LNNA) were protected against O2-induced convulsions. Selected cerebral amino acids including arginine were measured in control and O2 treated rats (6 ATA, 20 min) with or without drug pretreatment. After O2 exposure, the cerebral pools of glutamate, aspartate, and GABA decreased significantly while glutamine content increased relative to control (P < 0.05). After treatment with either enzyme inhibitor, glutamine, glutamate and aspartate concentrations were maintained near control levels. Remarkably, GABA depletion by O2 was not prevented despite protection from seizures by both pargyline and LNNA. The NO. precursor, arginine, was increased significantly in the brain by toxic O2 exposure, but both pargyline and LNNA inhibited this effect. Simultaneous norepinephrine measurements indicated that its storage substantially decreased during hyperoxia (P < 0.05), but this effect too was blocked by either pargyline or LNNA. These data indicate that protection against O2 by these inhibitors is not related to preservation of the GABA pool. More importantly, O2 dependent norepinephrine metabolism and NO. synthesis appear to be interactive during CNS O2 toxicity.
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PMID:Cerebral amino acid, norepinephrine and nitric oxide metabolism in CNS oxygen toxicity. 846 4


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