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)

Reactive oxygen species have been postulated to be a causal factor in the aging process due to their ability to inflict molecular damage. The role of the enzyme copper-zinc superoxide dismutase (Cu-Zn SOD; superoxide:superoxide oxidoreductase; EC 1.15.1.1), which scavenges superoxide anion radicals, as a longevity determinant was examined in transgenic Drosophila melanogaster. A genomic fragment containing the Drosophila Cu-Zn SOD gene was introduced into the germ cells via a P element containing Casper vector. In different transgenic lines, overexpression of SOD by 32-42% above normal had either a minor and/or an insignificant effect on life span of the flies and their ability to withstand experimental oxidative stress, induced by paraquat intake and exposure to hyperoxia (100% oxygen). Transgenics showing a small increase in mean life span also exhibited a corresponding improvement in their resistance to hyperoxia but not paraquat. The maximum life span of populations was not affected.
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PMID:Effects of Cu-Zn superoxide dismutase overexpression of life span and resistance to oxidative stress in transgenic Drosophila melanogaster. 844 64

High oxygen tension (hyperoxia) causes pulmonary cell death, involving apoptosis, necrosis, or mixed death phenotypes, though the underlying mechanisms remain unclear. In mouse lung endothelial cells (MLEC) hyperoxia activates both extrinsic (Fas-dependent) and intrinsic (mitochondria-dependent) apoptotic pathways. We examined the hypothesis that FLIP, an inhibitor of caspase-8, can protect endothelial cells against the lethal effects of hyperoxia. Hyperoxia caused the time-dependent downregulation of FLIP in MLEC. Overexpression of FLIP attenuated intracellular reactive oxygen species generation during hyperoxia exposure, by downregulating extracellular-regulated kinase-1/2 activation and p47(phox) expression. FLIP prevented hyperoxia-induced trafficking of the death-inducing signal complex from the Golgi apparatus to the plasma membrane. Furthermore, FLIP blocked the activations of caspase-8/Bid, caspases -3/-9, and inhibited the mitochondrial translocation and activation of Bax, resulting in protection against hyperoxia-induced cell death. Under normoxic conditions, FLIP expression increased the phosphorylation of p38 mitogen-activated protein kinase leading to increased phosphorylation of Bax during hyperoxic stress. Furthermore, FLIP expression markedly inhibited protein kinase C activation and expression of distinct protein kinase C isoforms (alpha, eta, and zeta), and stabilized an interaction of PKC with Bax. In conclusion, FLIP exerted novel inhibitory effects on extrinsic and intrinsic apoptotic pathways, which significantly protected endothelial cells from the lethal effects of hyperoxia.
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PMID:FLIP inhibits endothelial cell apoptosis during hyperoxia by suppressing Bax. 1744 7