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)

Clusterin is a widely expressed, well conserved, secreted glycoprotein, which is highly induced in tissues regressing as a consequence of apoptotic cell death in vivo. It has recently been shown that clusterin expression is only confined to surviving cells following the induction of apoptosis in vitro, suggesting that it is involved in cell survival rather than death. In the hypothesis that clusterin may be implicated in cellular responses to stress, clusterin gene expression was analyzed in the A431 human epidermoid cancer cell line following heat shock and oxidative stress. Our results show that both a transient heat shock (20 min at 42 degrees C) and various oxidative stresses, including hydrogen peroxide, superoxide anion, hyperoxia and UVA exposure, induce a strong increase in clusterin mRNA levels as assessed by northern blot. Nuclear run-on analysis suggests that transcriptional activation is involved in inducing clusterin mRNA in response to heat shock. Using pulse-chase analysis of control and heat shocked cells, it is shown that clusterin mRNA is translated and secreted, thus resulting in increased extracellular levels of the protein following heat shock. To investigate the function of clusterin in response to these stresses, clusterin anti-sense transfectants that stably express virtually no clusterin at the mRNA and protein level were generated in A431 cells. These anti-sense transfectants are shown to be highly sensitive to apoptotic cell death induced by heat shock or oxidative stress compared with wild-type A431 cells or control transfectants. Taken together, our results show that clusterin gene expression is induced in response to heat shock and oxidative stress in human A431 cells, and confers cellular protection against heat shock and oxidative stress.
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PMID:Clusterin gene expression mediates resistance to apoptotic cell death induced by heat shock and oxidative stress. 1008 4

Preclinical studies in the premature baboon evaluating the efficacy and potential toxicity of inhaled nitric oxide indicated a significant effect on astrocyte area density, suggesting phenotypic and functional changes in astrocytes upon exposure to nitric oxide. However, the effects of nitric oxide and oxygen, the two major therapeutic gases utilized in neonatal intensive care, on astrocyte morphology and function remain vastly unknown. Herein, we report that exposure of mouse neonatal cortical astrocytes to hyperoxia results in a proinflammatory phenotype and increase in proliferation without significant changes in cellular morphology or levels of intermediate filament proteins. The proinflammatory phenotype was evident by a significant increase in cellular levels of cyclooxygenase-2 and a concomitant increase in prostaglandin E(2) secretion, a decline in the intracellular and secreted levels of apolipoprotein E, and a significant increase in the intracellular levels of clusterin. This proinflammatory phenotype was not evident upon simultaneous exposure to hyperoxia and nitric oxide. These results suggest that exposure to nitric oxide in the setting of hyperoxia confers unrecognized beneficial effects by suppressing astrocytic inflammation.
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PMID:Nitric oxide counteracts the hyperoxia-induced proliferation and proinflammatory responses of mouse astrocytes. 2160 65