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)

The role of heme oxygenase (HO)-1 was evaluated in the oxygen-resistant hamster fibroblast cell line, O2R95, which moderately overexpress HO when compared with the parental cell line, HA-1. To suppress HO-1 expression, O2R95 were transfected with HO-1 antisense oligonucleotide or treated with tin-mesoporphyrin (SnMP). To increase HO-1 expression, cells were transfected with HO-1 cDNA in a pRC/cytomegalovirus (CMV) vector. All cells were challenged with a 48-h exposure to 95% O2 (hyperoxia). When HO activity was suppressed, O2R95 cells had significantly decreased cell viability, increased susceptibility to lipid peroxidation, and increased protein oxidation in hyperoxia. In contrast, further overexpression of HO-1 did not improve resistance to oxygen toxicity. Antisense-transfected cells and SnMP-treated cells with lowered HO activity showed increased levels of cellular heme compared with controls. In the HO-1 cDNA-transfected O2R95 cells, cellular heme was lowered compared with controls; however, cellular redox active iron levels were increased. We conclude that HO mediates cytoprotection to oxygen toxicity within a narrow range of expression. We speculate that this protective effect may be mediated in part through increased metabolism of the pro-oxidant heme but that higher levels of HO activity obviate protection by increased redox active iron release.
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PMID:Heme oxygenase-mediated resistance to oxygen toxicity in hamster fibroblasts. 916 65

Acute and chronic lung injury secondary to hyperoxia remains an important complication in critically ill patients, and, consequently, there is interest in developing strategies to protect the lung against hyperoxia. Heat shock proteins (HSPs) confer protection against a broad array of cytotoxic agents. In this study, we tested the hypothesis that increased expression of the 70-kDa HSP (HSP70) would protect cultured human respiratory epithelium against hyperoxia. Recombinant A549 cells were generated in which human HSP70 was increased by stable transfection with a plasmid containing human HSP70 cDNA under control of the cytomegalovirus promoter (A549-HSP70 cells). A549-HSP70 cells exposed to hyperoxia had greater acute survival rates and clonogenic capacity compared with wild-type A549 cells and with control cells stably transfected with the empty expression plasmid. Hyperoxia-mediated lipid peroxidation and ATP depletion were also attenuated in A549-HSP70 cells exposed to hyperoxia. Increased expression of HSP70 did not detectably alter mRNA levels of the intracellular antioxidants manganese superoxide dismutase, catalase, and glutathione peroxidase. Collectively, these data demonstrate a specific in vitro protective role for HSP70 against hyperoxia and suggest that potential mechanisms of protection involve attenuation of hyperoxia-mediated lipid peroxidation and ATP depletion.
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PMID:Increased expression of heat shock protein-70 protects A549 cells against hyperoxia. 975 17

Pulmonary oedema results from an imbalance between the forces driving fluid into the airspace and the biological mechanisms for its removal. In mice lacking the alpha-subunit of the amiloride-sensitive sodium channel (alphaENaC(-/-)), impaired sodium transport-mediated lung liquid clearance at birth results in neonatal death. Transgenic expression of alphaENaC driven by a cytomegalovirus (CMV) promoter (alphaENaC(-/-)Tg+) rescues the lethal pulmonary phenotype, but only partially restores respiratory sodium transport in vitro. To test whether this may also be true in vivo, and to assess the functional consequences of this defect on experimental pulmonary oedema, we measured respiratory transepithelial potential difference (PD) and alveolar fluid clearance (AFC), and quantified pulmonary oedema during experimental acute lung injury in these mice. Both respiratory PD and AFC were roughly 50% lower (P < 0.01) in alphaENaC(-/-)Tg+ than in control mice. This impairment was associated with a significantly larger increase of the wet/dry lung weight ratio in alphaENaC(-/-)Tg+ than in control mice, both after exposure to hyperoxia and thiourea. Moreover, the rate of resolution of thiourea-induced pulmonary oedema was more than three times slower (P < 0.001) in alphaENaC(-/-)Tg+ mice. alphaENaC(-/-)Tg+ mice represent the first model of a constitutively impaired respiratory transepithelial sodium transport, and provide direct evidence that this impairment facilitates pulmonary oedema in conscious freely moving animals. These data in mice strengthen indirect evidence provided by clinical studies, suggesting that defective respiratory transepithelial sodium transport may also facilitate pulmonary oedema in humans.
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PMID:Defective respiratory amiloride-sensitive sodium transport predisposes to pulmonary oedema and delays its resolution in mice. 1530 80

MicroRNAs (miRs) are small conserved RNA that regulate gene expression. Bioinformatic analysis of miRNA profiles during mouse lung development indicated a role for multiple miRNA, including miRNA-489. miR-489 increased on completion of alveolar septation [postnatal day 42 (P42)], associated with decreases in its conserved target genes insulin-like growth factor-1 (Igf1) and tenascin C (Tnc). We hypothesized that dysregulation of miR-489 and its target genes Igf1 and Tnc contribute to hyperoxia-induced abnormal lung development. C57BL/6 mice were exposed to normoxia (21%) or hyperoxia (85% O2) from P4 to P14, in combination with intranasal locked nucleic acid against miR-489 to inhibit miR-489, cytomegalovirus promoter (pCMV)-miR-489 to overexpress miR-489, or empty vector. Hyperoxia reduced miR-489 and increased Igf1 and Tnc. Locked nucleic acid against miR-489 improved lung development during hyperoxia and did not alter it during normoxia, whereas miR-489 overexpression inhibited lung development during normoxia. The 3' untranslated region in vitro reporter studies confirmed Igf1 and Tnc as targets of miR-489. While miR-489 was of epithelial origin and present in exosomes, its targets Igf1 and Tnc were produced by fibroblasts. Infants with bronchopulmonary dysplasia (BPD) had reduced lung miR-489 and increased Igf1 and Tnc compared with normal preterm or term infants. These results suggest increased miR-489 is an inhibitor of alveolar septation. During hyperoxia or BPD, reduced miR-489 and increased Igf1 and Tnc may be inadequate attempts at compensation. Further inhibition of miR-489 may permit alveolar septation to proceed. The use of specific miRNA antagonists or agonists may be a therapeutic strategy for inhibited alveolarization, such as in BPD.
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PMID:Regulation of alveolar septation by microRNA-489. 2671 45