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

Increased glucose utilization and hexokinase (HK)-II expression are adaptive features of lung cells exposed to hypoxia or hyperoxia. HK-II is the most regulated isoform of HK. Whether its overexpression could be protective against oxidative stress was explored in human lung epithelial-like (A549) cells. HK-II was overexpressed in A549 cells in a tetracycline-repressible retroviral vector system. Elevated expression of HK-II was confirmed by Western blot and activity measurements. Cell death caused by exposure to hyperoxia was decreased in HK-II-overexpressing cells. This effect was reversed when HK-II expression was suppressed with doxycycline. A similar protective effect was observed in HK-II-overexpressing cells after treatment with 1 mM hydrogen peroxide for 48 h. At baseline, fluorescence microscopy showed that overexpressed HK-II was localized to mitochondria. Electron microscopic studies showed that hyperoxia-exposed HK-II overexpressors had better-preserved and quantitatively smaller mitochondria than those in which the HK-II expression was suppressed or in the nontransduced A549 cells. Mitochondrial membrane potential was increased in HK-II-overexpressing cells exposed to hyperoxia compared with the nontransduced control cells under similar conditions. The present study demonstrates that HK-II protects human lung epithelial-like A549 cells against oxidative insults by protecting the mitochondria.
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PMID:Elevated expression of hexokinase II protects human lung epithelial-like A549 cells against oxidative injury. 1216 77

Preterm infants lack adequate surfactant production and often require oxygen support for adequate oxygenation. Prolonged oxygen treatment leads to the development of bronchopulmonary dysplasia (BPD), a disease process characterized by the blunting of alveolarization and proliferation of myofibroblasts. In the present study, we investigated metabolic adaptive changes in cultured fibroblasts isolated from immature (d18) and near-term (d21), fetal rat lungs in response to normoxic (21%) and hyperoxic (95%) exposures. We used the [1,2-13C2]D-glucose tracer and gas chromatography/mass spectrometry to characterize glucose carbon redistribution between the nucleic acid ribose, lactate, and palmitate synthetic pathways, and reverse transcriptase-polymerase chain reaction to assess adipose differentiation related protein (ADRP) mRNA expression in response to hyperoxic exposure. Exposure to hyperoxia at each passage caused decrease (*, p<0.05 vs. 21% O2) in ADRP mRNA expression in the d18 fibroblasts. This passage-dependent transdifferentiation is accompanied by a moderate (9-20%) increase in the synthesis of nucleic acid ribose from glucose through the non-oxidative steps of the pentose cycle. In contrast, d18 fibroblasts showed over an 85% decrease in the de novo synthesis of palmitate from glucose, while d21 fibroblasts showed a less pronounced 32-38% decrease in de novo lipid synthesis in hyperoxia-exposed cultures. It can be concluded from these studies that: (1) there is a maturation dependent sensitivity to hyperoxia; (2) transdifferentiation of flbroblast as demonstrated by changes in ADRP expression is accompanied by metabolic enzymes changes affecting ribose acid synthesis from glucose, and (3) hyperoxia specifically inhibits lipogenesis from glucose. Hyperoxia-induced metabolic changes thus play a key role in the transdifferentiation of lung fibroblasts to myofibroblasts and the pathogenesis of BPD.
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PMID:Oxygen-induced metabolic changes and transdifferentiation in immature fetal rat lung lipofibroblasts. 1240 71

Respiratory failure is a serious consequence of lung cell injury caused by treatment with high inhaled oxygen concentrations. Human lung microvascular endothelial cells (HLMVEC) are a principal target of hyperoxic injury (hyperoxia). Cell stress can cause release of ATP, and this extracellular nucleotide can activate purinoreceptors and mediate responses essential for survival. In this investigation, exposure of endothelial cells to an oxidative stress, hyperoxia, caused rapid but transient ATP release (20.03 +/- 2.00 nm/10(6) cells in 95% O(2) versus 0.08 +/- 0.01 nm/10(6) cells in 21% O2 at 30 min) into the extracellular milieu without a concomitant change in intracellular ATP. Endogenously produced extracellular ATP-enhanced mTOR-dependent uptake of glucose (3467 +/- 102 cpm/mg protein in 95% oxygen versus 2100 +/- 112 cpm/mg protein in control). Extracellular addition of ATP-activated important cell survival proteins like PI 3-kinase and extracellular-regulated kinase (ERK-1/2). These events were mediated primarily by P2Y receptors, specifically the P2Y2 and/or P2Y6 subclass of receptors. Extracellular ATP was required for the survival of HLMVEC in hyperoxia (55 +/- 10% surviving cells with extracellular ATP scavengers [apyrase + adenosine deaminase] versus 95 +/- 12% surviving cells without ATP scavengers at 4 d of hyperoxia). Incubation with ATP scavengers abolished ATP-dependent ERK phosphorylation stimulated by hyperoxia. Further, ERK activation also was found to be important for cell survival in hyperoxia, as treatment with PD98059 enhanced hyperoxia-mediated cell death. These findings demonstrate that ATP release and subsequent ATP-mediated signaling events are vital for survival of HLMVEC in hyperoxia.
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PMID:Extracellular ATP-mediated signaling for survival in hyperoxia-induced oxidative stress. 1476 47

Oxygen is critical to aerobic metabolism, but excessive oxygen (hyperoxia) causes cell injury and death. An oxygen-tolerant strain of HeLa cells, which proliferates even under 80% O2, termed "HeLa-80," was derived from wild-type HeLa cells ("HeLa-20") by selection for resistance to stepwise increases of oxygen partial pressure. Surprisingly, antioxidant defenses and susceptibility to oxidant-mediated killing do not differ between these two strains of HeLa cells. However, under both 20 and 80% O2, intracellular reactive oxygen species (ROS) production is significantly (approximately 2-fold) less in HeLa-80 cells. In both cell lines the source of ROS is evidently mitochondrial. Although HeLa-80 cells consume oxygen at the same rate as HeLa-20 cells, they consume less glucose and produce less lactic acid. Most importantly, the oxygen-tolerant HeLa-80 cells have significantly higher cytochrome c oxidase activity (approximately 2-fold), which may act to deplete upstream electron-rich intermediates responsible for ROS generation. Indeed, preferential inhibition of cytochrome c oxidase by treatment with n-methyl protoporphyrin (which selectively diminishes synthesis of heme a in cytochrome c oxidase) enhances ROS production and abrogates the oxygen tolerance of the HeLa-80 cells. Thus, it appears that the remarkable oxygen tolerance of these cells derives from tighter coupling of the electron transport chain.
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PMID:Oxygen tolerance and coupling of mitochondrial electron transport. 1532 48

We have shown that neural tube defects (NTD) in a mouse model of diabetic embryopathy are associated with deficient expression of Pax3, a gene required for neural tube closure. Hyperglycemia-induced oxidative stress is responsible. Before organogenesis, the avascular embryo is physiologically hypoxic (2-5% O(2)). Here we hypothesized that, because O(2) delivery is limited at this stage of development, excess glucose metabolism could accelerate the rate of O(2) consumption, thereby exacerbating the hypoxic state. Because hypoxia can increase mitochondrial superoxide production, excessive hypoxia may contribute to oxidative stress. To test this, we assayed O(2) flux, an indicator of O(2) availability, in embryos of glucose-injected hyperglycemic or saline-injected mice. O(2) flux was reduced by 30% in embryos of hyperglycemic mice. To test whether hypoxia replicates, and hyperoxia suppresses, the effects of maternal hyperglycemia, pregnant mice were housed in controlled O(2) chambers on embryonic day 7.5. Housing pregnant mice in 12% O(2), or induction of maternal hyperglycemia (>250 mg/dl), decreased Pax3 expression fivefold, and increased NTD eightfold. Conversely, housing pregnant diabetic mice in 30% O(2) significantly suppressed the effect of maternal diabetes to increase NTD. These effects of hypoxia appear to be the result of increased production of mitochondrial superoxide, as indicated by assay of lipid peroxidation, reduced glutathione, and H(2)O(2). Further support of this interpretation was the effect of antioxidants, which blocked the effects of maternal hypoxia, as well as hyperglycemia, on Pax3 expression and NTD. These observations suggest that maternal hyperglycemia depletes O(2) in the embryo and that this contributes to oxidative stress and the adverse effects of maternal hyperglycemia on embryo development.
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PMID:Hypoxic stress in diabetic pregnancy contributes to impaired embryo gene expression and defective development by inducing oxidative stress. 1592 21

The cores of rabbit plaques in vivo are hypoxic, suggesting that ATP depletion due to an insufficient supply of oxygen and nutrients could contribute to macrophage death in atherosclerotic plaques. During hypoxia, however, macrophages maintain ATP levels by anaerobic glycolysis. To directly assess ATP and glucose metabolites in plaques in vivo, we used bioluminescence imaging to map the concentrations of ATP, glucose, glycogen, and lactate in normal and atherosclerotic rabbit aortas in vivo. Hypoxia was assessed with NITP (7-(4'-(2-nitroimidazol-1-yl)-butyl)-theophylline). Normal aortas and plaques <500 microm thick were not hypoxic and had homogenous concentrations of energy metabolites. In plaques >500 microm thick, however, the cores were characterized by ATP depletion, low concentrations of glucose and glycogen, and a high concentration of lactate. A majority of ATP-depleted macrophages within the core were viable but severely hypoxic and glucose depleted. Hyperoxia in vitro reversed the ATP depletion in macrophages in viable areas of the core. Our findings suggest that ATP depletion contributes to the death of macrophages in atherosclerotic lesions and to the formation of a necrotic core.
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PMID:ATP depletion in macrophages in the core of advanced rabbit atherosclerotic plaques in vivo. 1640 94

High oxygen concentrations (hyperoxia), often required in the treatment of preterm infants and critically ill patients, cause lung injury, targeting especially the endothelium. Exposure of primary human lung microvascular endothelial cells (HLMVEC) to hyperoxia caused transient Akt activation after 60 min, as determined by Western blot analysis of phosphorylated Ser 473 of Akt. Akt phosphorylation was also increased after 24 h of hyperoxic exposure, which declined at 48 h. Adenoviral (Ad)-mediated expression of constitutively active myrAkt protected HLMVEC against hyperoxic injury. Cell death due to hyperoxia (95% O2, 8 days), which was primarily necrotic, was substantial in control and Ad-LacZ-transduced cells, but was diminished by almost half in myrAkt-transduced cells. Hyperoxia caused increased cellular glucose consumption, an effect that was amplified in cells transduced with myrAkt compared to the LacZ-transduced or the nontransduced controls. Increased glucose consumption in myrAkt-expressing cells was accompanied by increased phosphorylation of mTOR and p70 S6-kinase. Rapamycin treatment decreased glucose consumption in myrAkt-transduced cells to levels comparable to those in control and LacZ-transduced cells exposed to hyperoxia. Ultrastructural morphometric analyses demonstrated that mitochondria and endoplasmic reticulum were less swollen in myrAkt cells relative to controls exposed to hyperoxia. These studies demonstrate that early activation of Akt occurs in hyperoxia in HLMVEC. That this event is a beneficial response is suggested by the finding that constitutive activation of Akt protects against hyperoxic stress, at least in part, by maintaining mitochondrial integrity.
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PMID:Endothelial Akt activation by hyperoxia: role in cell survival. 1654 78

Embryonic stem cell lines are routinely selected and cultured in glucose and oxygen concentrations that are well above those of the intrauterine environment. Supraphysiological glucose and hyperoxia each increase oxidative stress, which could be detrimental to survival in vitro by inhibiting proliferation and/or inducing cell death. The aim of this study was to test whether isolation of new embryonic stem cell lines from murine blastocysts is improved by culture in physiological (5%) oxygen instead of approximately 20%, the concentration of oxygen in room air, or in media containing physiological (100 mg/dL) instead of 450 mg/dL glucose. We found that culturing in either physiological oxygen or physiological glucose improved the success of establishing new murine embryonic stem cell lines, and that culture when concentrations of both oxygen and glucose were physiological improved the success of establishing new lines more than culture in either alone. Physiological oxygen and glucose reduce oxidative stress, as determined by 2',7'-dichloro-dihydrofluorescein fluorescence. BrdU incorporation suggests that physiological oxygen and glucose increase the pool of proliferating cells. Cells isolated in physiological oxygen and glucose are capable of self-renewal and differentiation into all three germ layers in vitro. However, none of the culture conditions prevents cytogenetic instability with prolonged passage. These results suggest that culture of cells derived from murine blastocysts in physiological oxygen and glucose reduces oxidant stress, which increases the success of establishing new embryonic stem cell lines.
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PMID:Establishment of new mouse embryonic stem cell lines is improved by physiological glucose and oxygen. 1677 2

Cardiopulmonary bypass (CPB) is associated with surgical stress, hypothermia, hyperoxia, enhancement of neuroendocrine outflow, and administration of glucogenic catecholamines that are associated with glucogonolysis and glucogenesis that result in hyperglycemia. The hyperglycemic state during CPB has been associated with adverse outcomes, such as infection, neurological impairment, cardiac dysfunction, prolonged hospitalization, and higher mortality rates. This report justifies vigilant monitoring of blood glucose levels and a rational protocol for the treatment of hyperglycemia of all open heart surgical patients that may improve post-CPB surgical outcomes.
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PMID:Hyperglycemia as an effect of cardiopulmonary bypass: intra-operative glucose management. 1692 93

The aim of this study was to investigate the effects of an increase in the saturation of blood oxygen (SaO2) and/or serum glucose on photoreceptor sensitivity in normal subjects and in patients with diabetes mellitus. We monitored cone and rod sensitivity by recording dark-adaptation curves to both green and red test stimuli while inhaling either air (20% O2 + 80% N2) or 100% oxygen in 12 normal subjects and 12 diabetic patients with no (10) or mild (2) retinopathy. We also repeated the experiment in 10 of the normal subjects under hyperglycemia (mean serum glucose: 161 mg/dl). Results show that in normal subjects the dark-adapted cone sensitivity is improved by an increase in SaO2 or by hyperglycemia. Final rod sensitivity is unchanged during hyperoxia and during hyperglycemia when measured with a green test spot. However the kinetics of dark adaptation are altered during hyperglycemia, and an increase in final sensitivity is observed when measured with the red test spot. Inhalation of oxygen during hyperglycemia in normal subjects reduces cone sensitivity compared to that found during hyperglycemia alone (Pasteur effect). In diabetic subjects the dark-adapted cone threshold is comparable to that found in normal subjects, and sensitivity also increases with an increase in SaO2. The final rod threshold, however, is impaired compared to that of the control group, and rod sensitivity is improved by increasing the SaO2. The results suggest that the metabolism of rods and cones may differ in normal subjects: in cones, the rate of metabolism can be augmented by increasing the available oxygen or glucose, whereas rods appear more insensitive to increased blood oxygen saturation and hyperglycemia. In diabetic subjects, both cone and rod metabolism can be increased by supplemental oxygen, indicative of an early rod deficit. The study lends weight to the hypothesis that dark-adapted rods in diabetics are hypoxic before the onset of retinopathy.
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PMID:Hyperoxia, hyperglycemia, and photoreceptor sensitivity in normal and diabetic subjects. 1696 9


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