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 HAP1 protein (also known as APE/Ref-1) is a bifunctional human nuclear enzyme required for repair of apurinic/apyrimidinic sites in DNA and reactivation of oxidized proto-oncogene products. To gain insight into the biological roles of HAP1, the effect of expressing antisense HAP1 RNA in HeLa cells was determined. The constructs for antisense RNA expression consisted of either a full-length HAP1 cDNA or a genomic DNA fragment cloned downstream of the CMV promoter in pcDNAneo. Stable HeLa cell transfectants expressing HAP1 antisense RNA were found to express greatly reduced levels of the HAP1 protein compared to equivalent sense orientation and vector-only control transfectants. The antisense HAP1 transfectants exhibited a normal growth rate, cell morphology and plating efficiency, but were hypersensitive to killing by a wide range of DNA damaging agents, including methyl methanesulphonate, hydrogen peroxide, menadione, and paraquat. However, survival after UV irradiation was unchanged. The antisense transfectants were strikingly sensitive to changes in oxygen tension, exhibiting increased killing compared to controls following exposure to both hypoxia (1% oxygen) and hyperoxia (100% oxygen). Consistent with a requirement for HAP1 in protection against hypoxic stress, expression of the HAP1 protein was found to be induced in a time-dependent manner in human cells during growth under 1% oxygen. The possible involvement of a depletion of cellular glutathione being linked to the hypoxic stress-sensitive phenotype of the antisense HAP1 transfectants came from the finding that they also exhibited hypersensitivity to buthionine sulphoximine, an inhibitor of glutathione biosynthesis. We conclude that the HAP1 protein is a key factor in cellular protection against a wide variety of cellular stresses, including DNA damage and a change in oxygen tension.
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PMID:A role for the human DNA repair enzyme HAP1 in cellular protection against DNA damaging agents and hypoxic stress. 780 Apr 76

The rat pheochromocytoma cell line PC12 is useful for studying neuronal cell differentiation since this cell line differentiates into neuron-like cells in response to nerve growth factor (NGF). We demonstrated that PC12h cells, a subclone of PC12 cells, died under hyperoxia (50% O2). This cell death did not occur in the presence of antioxidant reagents. In the dead cells, DNA fragmentation and chromatin condensation were observed, suggesting that hyperoxia-induced apoptosis via reactive oxygen species (ROS). NGF effectively suppressed this hyperoxia-induced apoptosis. Accordingly, the amounts of bcl-2, a proto-oncogene product, increased in the cells rescued from apoptosis by NGF. Furthermore, bcl-2 antisense oligonucleotide canceled this rescuing effect of NGF. The present findings indicate that NGF rescues PC12h cells from hyperoxia-induced apoptosis via up-regulation of bcl-2.
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PMID:The rescuing effect of nerve growth factor is the result of up-regulation of bcl-2 in hyperoxia-induced apoptosis of a subclone of pheochromocytoma cells, PC12h. 930 89