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

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

Hyperoxia treatment has been known to induce neuronal and glial death in the developing central nervous system. Retinopathy of prematurity (ROP) is a devastating disease in premature infants and a major cause of childhood vision impairment. Studies indicate that, in addition to vascular injury, retinal neurons are also affected in ROP. Using an oxygen-induced retinopathy (OIR) mouse model for ROP, we have previously shown that deletion of the arginase 2 (A2) significantly reduced neuro-glial injury and improved retinal function. In the current study, we investigated the mechanism of A2 deficiency-mediated neuroprotection in the OIR retina. Hyperoxia treatment has been known to induce neuronal death in neonates. During the hyperoxia phase of OIR, a significant increase in the number of apoptotic cells was observed in the wild-type (WT) OIR retina compared with A2-deficient OIR. Mass spectrometric analysis showed alterations in polyamine metabolism in WT OIR retina. Further, increased expression level of spermine oxidase was observed in WT OIR retina, suggesting increased oxidation of polyamines in OIR retina. These changes were minimal in A2-deficient OIR retina. Treatment using the polyamine oxidase inhibitor, N, N'-bis (2, 3-butadienyl)-1, 4-butanediamine dihydrochloride, significantly improved neuronal survival during OIR treatment. Our data suggest that retinal arginase is involved in the hyperoxia-induced neuronal degeneration in the OIR model, through the regulation of polyamine metabolism.
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PMID:Arginase 2 deficiency reduces hyperoxia-mediated retinal neurodegeneration through the regulation of polyamine metabolism. 2455 90

Most mammalian tissue cells experience oxygen partial pressures in vivo equivalent to 1-6% O2 (i.e., physioxia). In standard cell culture, however, headspace O2 levels are usually not actively regulated and under these conditions are ~18%. This drives hyperoxia in cell culture media that can affect a wide variety of cellular activities and may compromise the ability of in vitro models to reproduce in vivo biology. Here, we review and discuss some specific O2-consuming organelles and enzymes, including mitochondria, NADPH oxidases, the transplasma membrane redox system, nitric oxide synthases, xanthine oxidase, and monoamine oxidase with respect to their sensitivities to O2 levels. Many of these produce reactive oxygen and/or nitrogen species (ROS/RNS) as either primary end products or byproducts and are acutely sensitive to O2 levels in the range from 1% to 18%. Interestingly, many of them are also transcriptional targets of hypoxia-inducible factors (HIFs) and chronic cell growth at physioxia versus 18% O2 may alter their expression. Aquaporins, which facilitate hydrogen peroxide diffusion into and out of cells, are also regulated by HIFs, indicating that O2 levels may affect intercellular communication via hydrogen peroxide. The O2 sensitivities of these important activities emphasize the importance of maintaining physioxia in culture.
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PMID:How Supraphysiological Oxygen Levels in Standard Cell Culture Affect Oxygen-Consuming Reactions. 3036 17


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