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

Exposure to high concentrations of oxygen (hyperoxia) can result in lung injury. The biochemical basis of this injury is poorly understood, but it is likely to include alterations in gene expression. Hyperoxia-induced (H-I) cDNAs have been molecularly cloned (Horowitz et al. J. Biol. Chem. 264: 7092-7095, 1989) from the lungs of an adult rabbit exposed to toxic levels of oxygen. One of them (H-I 1) was identified as encoding the tissue inhibitor of metalloproteinases (TIMP), a key regulatory protein of extracellular matrix turnover. Here we identify another clone (H-I 3) as encoding pulmonary surfactant apoprotein A (SP-A). We also show that in neonatal rabbits exposed to 100% oxygen for 96 h, the mRNAs corresponding to TIMP, SP-A, and another H-I gene are increased. These studies have begun to explore specific changes in gene expression associated with neonatal hyperoxic lung injury.
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PMID:Changes in gene expression in hyperoxia-induced neonatal lung injury. 168 50

Hyperoxic lung injury is an unfortunate consequence of ventilatory oxygen therapy that is necessary to sustain life in certain clinical situations. The biochemical events that accompany hyperoxia of the lung, and the molecular mechanisms underlying these events, are incompletely understood. To better understand hyperoxic lung injury, our laboratory has cloned a set of genes corresponding to mRNAs that increase in abundance in the lungs of hyperoxic rabbits. In this report, we focus on three hyperoxia-induced cDNA clones, which encode surfactant apoprotein A (SP-A), the tissue inhibitor of metalloproteinases (TIMP), and metallothionein. In situ hybridizations and RNA dot blots of isolated lung cell populations indicate that the abundance of mRNA encoding all three proteins is increased by hyperoxia in specific cell types. SP-A mRNA increases in type II alveolar epithelial cells and in bronchiolar epithelial cells. TIMP mRNA increases in interstitial fibroblasts, in chondrocytes of the cartilage surrounding airways, and in endothelial cells of a specific subset of vessels, probably venules. Metallothionein transcripts also increase in chondrocytes and pulmonary fibroblasts. A comparison of the increase in these mRNAs during hyperoxic exposure in adults and newborns indicates that adults respond faster and to a greater extent than newborns and suggests that the rate and extent of these increases is correlated with the time course and severity of the injury.
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PMID:Cell-specific alterations in expression of hyperoxia-induced mRNAs of lung. 195 78

Exposure to high concentrations of oxygen can result in tissue damage, particularly in the lung. Lung pathology induced by hyperoxia includes changes in lung cell populations and morphology. Presumably, alterations in gene expression underlie some of these cellular changes. In order to better understand the molecular basis of these events, a cDNA library was constructed from the mRNA of the lungs of a hyperoxia-exposed rabbit and differentially screened for clones corresponding to hyperoxia-induced messages. This approach has led to the isolation of four clones, three of which are presented in this communication. One clone corresponds to a message whose steady state levels were induced 6-fold and encodes the tissue inhibitor of metalloproteinases, a protein that plays a key role in the regulation of connective tissue turnover in some cells and potentiates erythroid development in others.
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PMID:Hyperoxic exposure alters gene expression in the lung. Induction of the tissue inhibitor of metalloproteinases mRNA and other mRNAs. 270 56

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