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

Hyperoxic stress alters expression of genes involved in extracellular matrix (ECM) remodeling. To identify novel ECM-associated gene products positively regulated by hyperoxia, rat kidney cells were exposed to 95% O2, and the complement of [35S]methionine-labeled, saponin-resistant, ECM-associated proteins was compared with normoxic controls. O2-stressed cells accumulated significantly greater ECM levels (approximately 3- to 4-fold that of control cells) of a 52-kDa glycoprotein (p52), recently identified as the matrix form of plasminogen activator inhibitor type 1 (PAI-1) (P.J. Higgins, P. Chaudhari, and M.P. Ryan. Biochem. J. 273: 651-658, 1991; P. J. Higgins, M. P. Ryan, R. Zeheb, T. D. Gelehrter, P. Chaudhari. J. Cell. Physiol. 143:321-329, 1990), which peaked at 48 h of exposure. Hyperoxia-associated increases in ECM p52(PAI-1) content reflected parallel elevations in p52(PAI-1) mRNA abundance. Similar results were obtained using secondary cultures of rat pulmonary fibroblasts. This 48-h period of maximal hyperoxia-induced p52(PAI-1) expression in vitro was used to design subsequent in vivo studies. Adult rats were exposed to 99% O2 for 24-50 h, and RNA was extracted from the pulmonary tissue of stressed and control animals. A 5- to 8-fold and 6- to 15-fold increase in lung p52(PAI-1) mRNA content was evident in hyperoxia-treated rats at 24 and 50 h, respectively. All of this increase occurred in the defined 3.2-kb species of rat p52(PAI-1) mRNA. Actin mRNA levels increased three- to sevenfold as a function of hyperoxic stress, whereas catalase and glyceraldehyde-3-phosphate dehydrogenase mRNA abundance was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hyperoxic stress elevates p52(PAI-1) mRNA abundance in cultured cells and adult rat pulmonary tissue. 836 24

To understand the molecular mechanisms that upregulate the activities of pulmonary antioxidant enzymes in adult rats during exposure to 85% oxygen, the relative contents of corresponding mRNA in normal and hyperoxic lungs were determined. Hyperoxic exposure drastically induced the expression of lung manganese-containing superoxide dismutase (MnSOD) mRNA. Maximal induction of MnSOD mRNA occurred at days 3 and 5 of exposure to hyperoxia, reaching a 600 and a 340% increase over the levels of air-exposed rats, respectively. In addition, hyperoxia induced lung mRNA for glucose-6-phosphate dehydrogenase, glutathione peroxidase, glyceraldehyde-3-phosphate dehydrogenase, alpha-tubulin, and gamma-actin to different extends at various days of exposure. Hyperoxia had little or no effect on the levels of mRNA for copper/zinc-containing superoxide dismutase (CuZnSOD), catalase, heat shock protein (HSP70), and creatine kinase. Nuclear run-on experiments showed that the transcriptional rate of the MnSOD gene is enhanced in hyperoxic rat lungs by approximately 400% at day 3 of exposure compared with that of controls. The specific activities of CuZnSOD and MnSOD in these lung samples per unit of lung protein or DNA were also determined. The activity of CuZnSOD in hyperoxic lungs was found to be unchanged compared with controls, except a 20% decrease at day 7 of exposure when standardized against protein content of lung homogenate. Changes of CuZnSOD activity were more dramatic in hyperoxic lungs (a 40% increase at days 3, 5, 7, and 14 of exposure) when enzyme activity was normalized using lung DNA content. Surprisingly, no proportional increase of lung MnSOD enzyme activity was observed at days 3 and 5 of oxygen exposure. The increase of MnSOD activity per unit of lung protein also did not parallel the increase in MnSOD protein content at days 5, 7, and 14 of exposure. These data suggest that, in addition to transcriptional activation, translational and/or posttranslational regulation of the MnSOD gene expression may play a critical role in controlling lung MnSOD activity on hyperoxic exposure.
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PMID:Antioxidant enzyme expression in rat lungs during hyperoxia. 896 16

We have shown previously with in vivo and in vitro animal models that the lens epithelium, in contrast to the nucleus, is remarkably resistant to hyperoxia. The main purpose of this study was to investigate the mRNA response of cultured human lens epithelial cells (LECs) to challenge by a high level of hyperbaric oxygen. Cells were treated for 3 hr with 50 atm of 99% O2, and then cultured normally for various times up to 11 days. Although the cells appeared normal immediately after the O2-treatment, they failed to grow and suffered 50% cell loss, as well as significant mitochondrial damage, during normal post-culture. Growth of the cells resumed after 3 days and by day 11, the number of O2-treated cells was the same as the controls. Remarkably, the 3 hr O2-treatment produced no immediate effects on either the cellular level of GSH, or on the activities of a number of antioxidant enzymes including glyceraldehyde-3-phosphate dehydrogenase, which is generally regarded as being highly sensitive to oxidation. In contrast, the activity of thioredoxin reductase (TrxR) was severely affected by the O2, decreasing by 51% after the 3 hr exposure. O2-induced death of the cells appeared to be caused by loss of ATP since a 31% decrease in ATP level occurred immediately after the O2-treatment, in spite of a 46% increase in lactate production. Analysis with real-time PCR showed a maximum 3-6-fold increase in mRNA levels 9 hr after the 3 hr O2-exposure for the enzymes heme oxygenase-1 (HO-1), MnSOD and TrxR1 (the cytoplasmic form of TrxR). These results were confirmed with the use of one-step RT-PCR and Northern blotting. Initial upregulation of message for HO-1 occurred a few hours before any upregulation of MnSOD could be detected, suggesting that release of free iron from the degradation of heme by HO-1 may have played a role in the upregulation of the dismutase. No significant changes in mRNA levels were observed for the antioxidant enzymes catalase, CuZnSOD, glutathione reductase and glutathione peroxidase, or for the antioxidant protein thioredoxin. Recovery of TrxR activity over a 4-day period appeared to parallel the return of the cells to a normal rate of growth. The results indicate that damaging effects of hyperoxia on cultured LECs occur primarily in the mitochondria, rather than in the cytoplasm. Cells avoid O2-induced cell death, and return to a normal rate of proliferation by upregulating mRNA levels for HO-1, MnSOD and TrxR1. It appears that full activity of TrxR1, an enzyme required for the production of deoxyribonucletides for DNA synthesis, is essential for the normal growth of O2-challenged LECs.
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PMID:Thioredoxin reductase may be essential for the normal growth of hyperbaric oxygen-treated human lens epithelial cells. 1564 22