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)

Cell death by oxidative stress has been proposed to be based on suicidal NAD depletion, typically followed by ATP depletion, caused by the NAD-consuming enzyme poly(ADP)ribose polymerase, which becomes activated by the presence of excessive DNA-strand breaks. In this study NAD+, NADH and ATP levels as well as DNA-strand breaks (assayed by alkaline elution) were determined in Chinese hamster ovary (CHO) cells treated with either H2O2 or hyperoxia to a level of more than 80% clonogenic cell killing. With H2O2 extensive DNA damage and NAD depletion were observed, while at a higher H2O2 dosage ATP also became depleted. In agreement with results of others, the poly(ADP)ribose polymerase inhibitor 3-aminobenzamide completely prevented NAD depletion. However, both H2O2-induced ATP depletion and cell killing were unaffected by the inhibitor, suggesting that ATP depletion may be a more critical factor than NAD depletion in H2O2-induced killing of CHO cells. With hyperoxia, only moderate DNA damage (2 X background) and no NAD depletion were observed, whereas ATP became largely (70%) depleted. We conclude that (1) there is no direct relation between ATP and NAD depletion in CHO cells subjected to toxic doses of H2O2 or hyperoxia; (2) H2O2-induced NAD depletion is not by itself sufficient to kill CHO cells; (3) killing of CHO cells by hyperoxia is not due to NAD depletion, but may be due to depletion of ATP.
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PMID:Effects of lethal exposure to hyperoxia and to hydrogen peroxide on NAD(H) and ATP pools in Chinese hamster ovary cells. 277 Jul 61

Hyperoxia induces extensive DNA damage and lung cell death by apoptotic and nonapoptotic pathways. We analyzed the regulation of Poly(ADP-ribose)polymerase-1 (PARP-1), a nuclear enzyme activated by DNA damage, and its relation to cell death during hyperoxia in vitro and in vivo. In lung epithelial-derived A549 cells, which are known to die by necrosis when exposed to oxygen, a minimal amount of PARP-1 was cleaved, correlating with the absence of active caspase-3. Conversely, in primary lung fibroblasts, which die mainly by apoptosis, the complete cleavage of PARP-1 was concomitant to the induction of active caspase-3, as assessed by Western blot and caspase activity. Blockade of caspase activity by Z-VAD reduced the amount of cleaved PARP-1 in fibroblasts. Hyperoxia induced PARP activity in both cell types, as revealed by poly-ADP-ribose accumulation. In A549 cells, the final outcome of necrosis was dependent on PARP activity because it was prevented by the PARP inhibitor 3-aminobenzamide. In contrast, apoptosis of lung fibroblasts was not sensitive to 3-aminobenzamide and was not affected by PARP-1 deletion. In vivo, despite evidence of PARP activation in hyperoxia-exposed mouse lungs, absence of PARP-1 did not change the extent of lung damage, arguing for redundant oxidative stress-induced cell death pathways.
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PMID:Poly(ADP-ribose)polymerase activation mediates lung epithelial cell death in vitro but is not essential in hyperoxia-induced lung injury. 1615 Oct 53