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)

Undernutrition may exacerbate hyperoxia-induced lung injury, a finding that may be of significance in the early clinical management of the premature human infant. Addressing this specific problem, we found that 72 h of food restriction in guinea pig pups delivered 3 days preterm increased mortality rates among pups exposed to 95% oxygen (8/18) and yet had no effect on 21% oxygen (air)-exposed pups (0/10). Reduced tolerance of hyperoxic conditions was not, however, associated with increased lung injury, assessed as pulmonary microvascular leakage. Pulmonary antioxidant enzyme activities [Cu,Zn superoxide dismutase (SOD), Mn SOD, glutathione peroxidase, and catalase] were unaltered by starvation or hyperoxia. Lung glutathione concentration was slightly decreased after food restriction, whereas hyperoxic exposure did not change either lung or bronchoalveolar lavage fluid glutathione concentrations or lung antioxidant enzyme activities. Increased susceptibility to the lethal effects of oxygen in the starved preterm guinea pig pup could not be attributed to a deficiency of pulmonary antioxidant defenses.
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PMID:Effect of food restriction on hyperoxia-induced lung injury in preterm guinea pig. 141 61

Emphysema in humans takes several different forms: centrilobular, panacinar, paraseptal, and airspace enlargement with fibrosis. The varying morphologic and background features of these forms of emphysema suggest that they differ in pathogenesis. Elastic fiber rupture and fraying are a feature of emphysema. Experimental emphysema may be induced by human neutrophil elastase and other elastolytic enzymes but not by nonelastolytic proteases. Disruption of elastic fibers also appears to be the underlying feature of lathyrogen-induced airspace enlargement and of the emphysema in the blotchy mouse. However, there is no evidence of elastic fiber destruction in cadmium-induced airspace enlargement with fibrosis or in emphysema associated with hyperoxia or severe starvation. Thus, elastic fiber disruption is not common to all forms of experimental emphysema. We posit that airspace enlargement may be a stereotyped response of the lungs to different injuries. Emphysema can be induced in experimental animals by repeated induction of pulmonary neutrophilia. However, the evidence for involvement of neutrophil elastase in human emphysema is not clear: there are studies using a variety of approaches that weigh on both sides of the question. There is also in vitro evidence that alveolar macrophages can degrade elastin or elastic fibers with which they are in contact by means of a metalloelastase or the cooperative action of plasminogen activator and an acid cysteine protease. We conclude that the pathogenesis of emphysema is complex. Neutrophil elastase likely plays a major role in the development of some forms of emphysema, but our understanding of the interactions between the alveolar walls and neutrophils is still fragmentary.
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PMID:Putative role of neutrophil elastase in the pathogenesis of emphysema. 206 48

1. Incubation of Escherichia coli with 0.7 mM doxorubicin in MBS-glucose medium resulted in complete growth inhibition, an inhibition that was blocked by placing specific amino acids (AA) in the medium. 2. The mechanism of protection by AA was similar to that reported previously for cells poisoned by hyperoxia and by paraquat, e.g. of 20 common AA, ten percent, ten do not and the branched-chair AA are among those required for inhibition. 3. Unlike hyperoxia and paraquot stringency which caused elevation of intracellular concentrations of guanosine tetraphosphate (ppGpp), doxorubicin inhibition did not elevate ppGpp. 4. Concentrations of ppGpp were increased by isoleucine starvation as expected, and the subsequent addition of doxorubicin did not abolish that increase; however, pretreatment with doxorubicin prevented the induction of stringency by isoleucine starvation. 5. This suggests that doxorubicin directly inhibits ppGpp synthesis or protein biosynthesis to leave tRNA loaded as is the case with chloramphenicol.
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PMID:Protection by selective amino acid solutions against doxorubicin induced growth inhibition of Escherichia coli. 755 72

We tested the effect of moderate food or water deprivation and a combination of the two on sensitivity to hyperoxia-induced seizures in rats. Seventy rats with chronic cortical electrodes were exposed to seven experimental protocols: starvation, dehydration or a combination of both for 24 or 36 h, prior to exposure to 0.5 Mp(a)O2. Blood glucose and hematocrit were measured before and after exposure to hyperbaric oxygen (HBO). Starvation and dehydration significantly prolonged the latent period to the onset of hyperoxia-induced seizures (P < 0.05 in the Tukey test), in a dose-related manner. Our results suggest that deprivation of food or water, prior to exposure to HBO, may postpone the development of hyperoxia-induced seizures.
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PMID:Starvation and dehydration attenuate CNS oxygen toxicity in rats. 924 77

Induction of cytochrome P450 2E1 (CYP2E1) has been shown to occur through two distinct mechanisms. The first is seen by treatment of rats with acetone, pyrazole, and 4-methyl-pyrazole, which induces CYP2E1 protein without affecting the mRNA level. The second is observed in starvation, diabetes, and obesity, in which an increase of CYP2E1 protein is associated with an increase of the CYP2E1 mRNA. It has been reported by (Tindberg and Ingelman-Sundberg 1989) that hyperoxic exposure (95% O2) induced a several-fold increase of CYP2E1 protein in both the liver and lung of exposed rats without affecting the level of CYP2E1 mRNA. During the course of our previous study which demonstrated hyperoxia-induced specific pretranslational induction of CYP1A1/2 in the liver and CYP1A1 in the lung, we observed a progressive increase of hepatic CYP2E1 mRNA in animals of the hyperoxia group. Hyperoxia is accompanied by some degree of starvation and our earlier experiments were conducted with rats of significantly greater body weight than those used by Tindberg and Ingelman-Sundberg (260 vs 150 g). Thus we reevaluated the changes of CYP2E1 in the current study with the use of food-restricted control, and by utilizing rats of comparable weight (approximately 150 g) to that utilized by Tindberg and Ingelman-Sundberg. The results obtained in the present study showed that there was a significant increase in the levels of hepatic CYP2E1 mRNA, protein, and p-nitrophenol hydroxylase activity in the food-restricted control group compared to the untreated controls. Rats from the hyperoxia group also demonstrated a similar increase of these three parameters in their livers but showed no significant difference compared with the results of the food-restricted control group. Rats weighing approximately 260 g were also examined with similar food restriction and hyperoxia, and the results were essentially similar to those obtained with the younger rats. The lungs of rats from food-restricted control and hyperoxia groups showed no increase of any of the CYP2E1 parameters. The results obtained in the current study, therefore, indicate that hyperoxia has no effect on CYP2E1 expression in both the liver and lung. Increased CYP2E1 mRNA, protein, and p-nitrophenol hydroxylase activity seen in the liver of rats, but not in the lungs, are consistent with the notion that undernutrition during hyperoxia is the underlying mechanism for this induction.
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PMID:Undernutrition during hyperoxic exposure induces CYP2E1 in rat liver. 936 41

Hypoxia is known to stimulate vascular growth by up-regulating vascular endothelial growth factor (VEGF), but little is known about the function of hypoxia in the development of the coronary vasculature, and the relationship between hypoxia and VEGF in this event. To test the effects of hypoxia and VEGF on coronary vasculogenesis/angiogenesis in the developing heart, ventricles from 6-day-old quail embryos were cultured on three-dimensional collagen gels. After 2 days of growth in normal medium and 1 day of starvation in low serum medium (0.5% fetal bovine serum), the heart explants were further cultured under various oxygen levels for another 24, 48, and 72 hr. Angioblasts and endothelial cells, which migrated out from the heart explants, were identified by QH1 antibody using immunofluorescence and confocal microscopy. In the normoxic culture environment, the endothelial cells began to proliferate and migrate out from the heart explants after 3 days of growth; they formed tubes mainly after another 72 hr. In contrast, this vascular growth was accelerated under hypoxic conditions, as evidenced by increased tube formation with significant differences observed at 48 hr. On the other hand, hyperoxia delayed this process. Reverse transcription-polymerase chain reaction results indicated that VEGF (including VEGF(122), VEGF(166), and VEGF(190)) was up-regulated in the heart explants under hypoxia and down-regulated under hyperoxia. VEGF neutralizing antibody added to the culture medium partially blocked this vascular growth. We conclude from this study that hypoxia can stimulate or up-regulate coronary vasculogenesis/angiogenesis and that VEGF signaling plays a major role in this event. Dev Dyn 1999;216:28-36.
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PMID:Stimulation of coronary vasculogenesis/angiogenesis by hypoxia in cultured embryonic hearts. 1047 63

To test whether heavy accumulation of ceroid/lipofuscin can disturb important functions of the lysosomal system, AG-1518 human fibroblasts, ceroid/lipofuscin-loaded (following prolonged culture at normobaric hyperoxia) or not, were exposed to amino acid starvation. Ceroid/lipofuscin-loading resulted in decreased cellular survival. Also, there was an inverse relationship between amounts of ceroid/lipofuscin and the survival time of individual cells within the same cultures. Ceroid/lipofuscin-loaded fibroblasts displayed diminished autophagocytotic capacity, as demonstrated by electron microscopy and by treatment of cell cultures with NH4Cl (which inhibits autophagocytotic degradation by increasing intralysosomal pH) for 1 week before ensuing starvation. The latter treatment increased survival of control cells (due to deposition of nondegraded autophagocytosed material before start of starvation), but not that of ceroid/lipofuscin-loaded cells. Moreover, when NH4Cl treatment was combined with starvation, both groups of cells showed approximately the same shortened survival times, testifying to the causal relationship between diminished autophagocytosis and decreased survival of starving ceroid/lipofuscin-loaded cells. We hypothesize that large amounts of undegradable ceroid/lipofuscin within the acidic vacuolar compartment may interfere with lysosomal function, resulting in poor renewal of long-lived proteins and worn-out/damaged organelles, decreased adaptability, and cell death.
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PMID:Ceroid/lipofuscin-loaded human fibroblasts show decreased survival time and diminished autophagocytosis during amino acid starvation. 1067 48

The purpose of this study was to understand the nature of the biochemical and physiological variations between genetically different lines of Drosophila melanogaster. Selection for early or delayed reproduction has given rise to lines with substantial and heritable differences in longevity. The hypotheses tested were that either: (i) a compensatory slowing of metabolism, (ii) increased antioxidative enzyme activities, or (iii) elevated resistance to stressful conditions underlie these differences in longevity. The metabolic rate, metabolic potential (i.e. total amount of oxygen consumed during average lifespan) and speed of walking were all greater in long-lived than in short-lived flies, but there was no enhancement of antioxidant defenses. In fact, catalase activity was significantly lower in the long-lived flies. Long life was largely maintained under heat stress and starvation conditions, and was maintained to a lesser extent upon exposure to paraquat, a superoxide radical generator. In contrast, the 'short-lived' flies had a longer lifespan under cold stress and hyperoxia, also an inducer of radical generation. These results contradict the first two hypotheses and suggest that alleles underlying either long or short life are linked with enhanced resistance to specific kinds of stress, which may account for the preservation of these alleles in the parental population.
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PMID:Antioxidant status and stress resistance in long- and short-lived lines of Drosophila melanogaster. 1125 Jan 17

Apolipoprotein E (apoE) mediates the hepatic clearance of plasma lipoproteins, facilitates cholesterol efflux from macrophages and aids neuronal lipid transport. ApoE is expressed at high levels in hepatocytes, macrophages and astrocytes. In the present study, we identify nuclear and cytosolic pools of apoE in human fibroblasts. Fibroblast apoE mRNA and protein levels were up-regulated during staurosporine-induced apoptosis and this was correlated with increased caspase-3 activity and apoptotic morphological alterations. Because the transcription of apoE and specific pro-apoptotic genes is regulated by the nuclear receptor LXR (liver X receptor) alpha, we analysed LXRalpha mRNA expression by quantitative real-time PCR and found it to be increased before apoE mRNA induction. The expression of ABCA1 (ATP-binding cassette transporter A1) mRNA, which is also regulated by LXRalpha, was increased in parallel with apoE mRNA, indicating that LXRalpha probably promotes apoE and ABCA1 transcription during apoptosis. Fibroblast apoE levels were increased under conditions of serum-starvation-induced growth arrest and hyperoxia-induced senescence. In both cases, an increased nuclear apoE level was observed, particularly in cells that accumulated lipofuscin. Nuclear apoE was translocated to the cytosol when mitotic nuclear disassembly occurred and this was associated with an increase in total cellular apoE levels. ApoE amino acid sequence analysis indicated several potential sites for phosphorylation. In vivo studies, using 32P-labelling and immunoprecipitation, revealed that fibroblast apoE can be phosphorylated. These studies reveal novel associations and potential roles for apoE in fundamental cellular processes.
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PMID:Induction of fibroblast apolipoprotein E expression during apoptosis, starvation-induced growth arrest and mitosis. 1465 20

Increased Apolipoprotein D (ApoD) expression has been reported in various neurological disorders, including Alzheimer's disease, schizophrenia, and stroke, and in the aging brain . However, whether ApoD is toxic or a defense is unknown. In a screen to identify genes that protect Drosophila against acute oxidative stress, we isolated a fly homolog of ApoD, Glial Lazarillo (GLaz). In independent transgenic lines, overexpression of GLaz resulted in increased resistance to hyperoxia (100% O(2)) as well as a 29% extension of lifespan under normoxia. These flies also displayed marked improvements in climbing and walking ability after sublethal exposure to hyperoxia. Overexpression of Glaz also increased resistance to starvation without altering lipid or protein content. To determine whether GLaz might be important in protection against reperfusion injury, we subjected the flies to hypoxia, followed by recovery under normoxia. Overexpression of GLaz was protective against behavioral deficits caused in normal flies by this ischemia/reperfusion paradigm. This and the accompanying paper by Sanchez et al. (in this issue of Current Biology) are the first to manipulate the levels of an ApoD homolog in a model organism. Our data suggest that human ApoD may play a protective role and thus may constitute a therapeutic target to counteract certain neurological diseases.
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PMID:Overexpression of a Drosophila homolog of apolipoprotein D leads to increased stress resistance and extended lifespan. 1658 12


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