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

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

The intraperitoneal administration of methylcyclopentadienyl manganese tricarbonyl (MMT) and cyclophosphamide, exposure to an aerosol of cadmium chloride, intravenous administration of oleic acid, and intratracheal instillation of bleomycin to young female BALB/c mice or CD/CR rats result in acute lung injury. Pulmonary morphology and lung collagen content were examined in animals treated with these chemicals alone or in combination with an elevated oxygen concentration (80%) in the inspired air. In mice, the development of fibrosis could be significantly enhanced if animals treated with MMT, cadmium chloride, cyclophosphamide, or bleomycin were exposed to 80% oxygen immediately following exposure to these agents. In rats only cyclophosphamide- and bleomycin-induced acute lung injury was potentiated by hyperoxia, resulting in significant enhancement of lung collagen content. The pathogenesis responsible for this differential species response of pulmonary injury to hyperoxia remains to be investigated.
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PMID:Potentiating effects of oxygen in lungs damaged by methylcyclopentadienyl manganese tricarbonyl, cadmium chloride, oleic acid, and antitumor drugs. 618 66

Acute exposure to hyperoxia results in well-described pathophysiologic responses in the lungs, beginning with subtle, subcellular changes and ending with severe pulmonary inflammation and edema. The biologic events that underlie or accompany this injury are not well understood. Our previous studies in rabbits have shown that hyperoxia induces large increases in the mRNAs encoding metallothionein (MT) and the tissue inhibitor of metalloproteinases (TIMP-I). Here we report studies of hyperoxic lung injury in two strains of mouse that differ in their relative resistance to O2 toxicity. O2-sensitive (C57BL/6J) mice and O2-resistant (C3H/HeJ) mice were exposed to 100% O2 for up to 96 h. Lung mRNAs were assayed by primer extension and slot blot hybridization. By 72 h of hyperoxia, the sensitive strain showed large increases in MT-I, MT-II, and TIMP-I mRNAs. The resistant strain showed similar changes but with a 24-h delay. In situ hybridization demonstrated that hyperoxic lung injury was accompanied by obvious increases in TIMP-I and MT transcripts in cells surrounding arteries and large airways, where many inflammatory cells were localized. With prolonged exposure, hybridization to MT transcripts had spread throughout lung parenchyma. The two strains showed the same patterns of in situ hybridization for TIMP-I and MT transcripts but, as with the whole lung homogenates, followed a different time course. Corresponding increases in MT protein were shown to occur, using a cadmium binding assay and by immunohistochemistry. The strong spatial correlation between the presence of localized inflammation and increased TIMP-I and MT expression further supports the importance of TIMP-I and MT in acute lung injury.
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PMID:Increased expression of tissue inhibitor of metalloproteinases (TIMP-I) and metallothionein in murine lungs after hyperoxic exposure. 811 Apr 67

Alveolar epithelial type II cells (AEIIC) were isolated from male Lewis rats following repeated in vivo cadmium aerosol exposure and were subsequently evaluated for their oxidant resistance in vitro. AEIIC from Cd-adapted animals removed a greater proportion of hydrogen peroxide from the extracellular milieu and incurred less oxidant-induced cytotoxicity than AEIIC from air controls. This altered response to oxidants occurred coincident with changes in cellular resistance factors. A two-fold increase in glutathione peroxidase activity and a 1.5-fold increase in the activities of glutathione reductase and catalase were observed in Cd-adapted AEIIC compared to control cells. These cells also exhibited a dramatic induction of metallothionein (MT), a thiol-rich protein known to scavenge free radicals in vitro. MT concentration increased as a function of exposure number. MT was localized within the nucleus and cytoplasm of AEIIC by immunocytochemical techniques. MT positive cells showed a wide variation of MT content, particularly in the nucleus. The biochemical and physiological features of these AEIIC may explain, in part, why animals pretreated with Cd aerosols develop cross-tolerance to hyperoxia.
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PMID:Increased oxidant resistance of alveolar epithelial type II cells. Isolated from rats following repeated exposure to cadmium aerosols. 855 67

The gene expression of heme oxygenase-1 (HO-1) was studied in mammalian cell lines exposed to hyperoxia. Northern blot analysis demonstrated that hyperoxic exposure increased the HO-1 mRNA levels in various types of cells, including human hepatoma (HepG2) cells. This increase was time- and dose-dependent, and reversible. The HO-1 mRNA levels in HepG2 cells were increased to 2.3- and 4.2-fold of the control by hyperoxic exposure of 6 and 23 h, respectively. Cycloheximide and actinomycin D inhibited the increases in the HO-1 mRNA level produced by hyperoxia, indicating that response to hyperoxia is dependent on de novo protein synthesis and mRNA transcription. Antioxidants, desferrioxamine (DES) and o-phenanthroline (OP) partially inhibited the HO-1 mRNA elevation by hyperoxia. In addition to hyperoxia, sodium arsenite (NaAsO2), cadmium chloride (CdCl(2)) and hydrogen peroxide (H2O2), which are reactive oxygen intermediates (ROI) generators, increased the HO-1 mRNA level by 11-, 22- and 2.5-fold, respectively. OP, an antioxidant and a bivalent metal chelator, blocked the HO-1 mRNA elevation induced either by hyperoxia or by the three ROI generators. In contrast to OP, N-acetylcysteine (NAC), an antioxidant and membrane-permeable reducing reagent, enhanced the HO-1 mRNA elevation induced by hyperoxia, although NAC inhibited the mRNA elevation induced by NaAsO2, CdCl2 and H2O2. These results indicate that oxygen tension regulates HO-1 gene expression and suggest that hyperoxia-specific and redox-sensitive regulators may be involved in hyperoxia-mediated HO-1 gene expression.
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PMID:Oxygen tension regulates heme oxygenase-1 gene expression in mammalian cell lines. 974 10

Metallothionein (MT) is a ubiquitous, cysteine-rich, metal-binding protein. MT synthesis is induced by various stimuli such as cadmium, mercury, zinc, oxidative stress, glucocorticoid, and anticancer agents. Recently, transgenic mice with loss-of-function mutations in the MT-I/-II genes were established. It has been assumed that MT plays a role in the detoxification of heavy metals. In recent studies using MT-null mice, the ability of MT to protect against cadmium-induced renal, liver and bone injuries has been confirmed. Moreover, MT is also capable of scavenging oxygen free radicals. MT is involved in the protection of tissues against various forms of oxidative injury, including radiation, lipid peroxidation, oxidative stress caused by anticancer drugs, and conditions of hyperoxia. However, MT still lacks an established biological function. Unexpectedly, the MT-null mice were apparently in good health, and the critical biological roles of MT have been questioned. MT seems to be a protective protein produced in response to a variety of stresses. Here, current studies on the protective roles of MT against toxicity of heavy metals and reactive oxygen species are reviewed, and the putative biological functions of MT are discussed.
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PMID:Recent studies on metallothionein: protection against toxicity of heavy metals and oxygen free radicals. 1249 22

We have investigated the effects of preconditioning pheochromocytoma (PC12) cells with intermittent hypoxia (IH) on transmitter release during acute hypoxia. Cell cultures were exposed to either alternating cycles of hypoxia (1% O(2) + 5% CO(2); 30 s/cycle) and normoxia (21% O(2) + 5% CO(2); 3 min/cycle) for 15 or 60 cycles or normoxia alone (control) for similar durations. Control and IH cells were challenged with either hyperoxia (basal release) or acute hypoxia (Po(2) of approximately 35 Torr) for 5 min, and the amounts of dopamine (DA) and acetylcholine (ACh) released in the medium were determined by HPLC combined with electrochemical detection. Hypoxia augmented DA (approximately 80%) but not ACh release in naive cells, whereas, in IH-conditioned cells, it further enhanced DA release (ranging from 120 to approximately 145%) and facilitated ACh release (approximately 30%). Hypoxia-evoked augmentation of transmitter release was not seen in cells conditioned with sustained hypoxia. IH-induced increase in DA but not IH-induced ACh release during hypoxia was partially inhibited by cadmium chloride (100 microM), a voltage-gated Ca(2+) channel blocker. By contrast, 2-aminoethoxydiphenylborate (75 microM), a blocker of inositol 1,4,5-trisphosphate (IP(3)) receptors, and N-acetyl-L-cysteine (300 microM), a potent scavenger of reactive oxygen species, either attenuated or abolished IH-evoked augmentation of transmitter release during hypoxia. Together, the above results demonstrate that IH conditioning increases hypoxia-evoked neurotransmitter release from PC12 cells via mechanisms involving mobilization of Ca(2+) from intracellular stores through activation of IP(3) receptors. Our findings also suggest that oxidative stress plays a central role in IH-induced augmentation of transmitter release from PC12 cells during acute hypoxia.
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PMID:Facilitation of dopamine and acetylcholine release by intermittent hypoxia in PC12 cells: involvement of calcium and reactive oxygen species. 1465 41

Heavy metals are essential components of many biological processes but are toxic at high concentrations. Our results illustrate that when metal homeostasis is compromised by a mutation in the metal-responsive transcription factor (MTF-1), the life-span is shortened. In contrast, MTF-1 overexpression results in resistant flies with prolonged longevity on iron or cadmium-supplemented media but shortened life-span on zinc-supplemented medium. This effect was mediated by the overexpression of MTF-1 in specific tissues, such as the gut, hemocytes and in particular in neurons, indicating that these tissues are particularly sensitive to the perturbance of metal homeostasis. Further, MTF-1 overexpression in a neuron-specific manner protects flies against hyperoxia and prolongs the life-span of Cu/Zn superoxide dismutase-deficient flies, suggesting the presence of a common mechanism for protection against both oxidative stress and metal toxicity. Finally, normal life-span is extended up to 40% upon MTF-1 overexpression in either the peripheral nervous system or motorneurons. These results document the tissue-specific import of heavy metal toxicity and oxidative damage in aging and life-span determination.
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PMID:Overexpression of metal-responsive transcription factor (MTF-1) in Drosophila melanogaster ameliorates life-span reductions associated with oxidative stress and metal toxicity. 1877 84