Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ability of niacin to relieve the growth-inhibiting effect of hyperoxia on Escherichia coli can be attributed to the dioxygen sensitivity of quinolinate synthetase. The activity of this enzyme within E. coli was diminished by exposure of the cells to 4.2 atm O2, while the activity in extracts was rapidly decreased by 0.2 atm O2. Neither catalase nor superoxide dismutase afforded detectable protection against the inactivating effect of O2, indicating that H2O2 and O2- were not significant intermediates in this process. Nevertheless, H2O2 at 1.0 mM did inactivate quinolinate synthetase, even under anaerobic conditions and in the absence of catalatic activity which might have generated O2. Addition of paraquat to aerobic cultures of E. coli caused an inactivation of quinolinate synthetase, which may be explained in terms of an increase in the production of H2O2. The O2-dependent inactivation of quinolinate synthetase in extracts was gradually reversed during anaerobic incubation and this reactivation was blocked by alpha, alpha'-dipyridyl or by 1,10-phenanthroline. The sequence of the quinolinate synthetase "A" protein contains a--cys-w-x-cys-y-z-cys--sequence, which is characteristic of (Fe-S)4-containing proteins. This sequence, together with the effect of the Fe(II)-chelating agents, suggests that the O2-sensitive site of quinolinate synthetase is an iron-sulfur cluster which is essential for the dehydration reaction catalyzed by the A protein.
 ...
PMID:Quinolinate synthetase: the oxygen-sensitive site of de novo NAD(P)+ biosynthesis. 184 9

The efficacy of niacin in protecting rats from normobaric hyperoxia was evaluated in vivo by exposing niacin treated animals and controls to greater than 95% O2 for 96 hours. The vitamin was also evaluated as a possible free radical scavenger in vitro using an Fe-ascorbate initiated microsomal lipid peroxidation system. No protective effects were observed in vivo either in mortality or in differences in lung wet and dry weights of the niacin treated rats when compared to controls. Niacin in varying concentrations also did not decrease lipid peroxidation in the microsomal systems. Although this vitamin has been reported to protect animals from paraquat toxicity when given intraperitoneally once daily, niacin administered in similar doses does not appear to protect rats from hyperoxia.
 ...
PMID:Inability of niacin to protect from in vivo hyperoxia or in vitro microsomal lipid peroxidation. 718 25

Sublethal exposure to hyperoxia in vivo induces oxidative damage that leads to destruction of the pulmonary endothelium, pleural effusion, and eventual pulmonary fibrosis. DNA is a potential target for reactive oxygen species in this system; the principle types of damage to DNA during hyperoxia are single-strand breaks and oxidant damage to bases. Poly(ADP-ribosyl)ation, a posttranslational modification of nuclear proteins, is stimulated by strand breaks in DNA and is required for effective repair of many types of DNA lesions. In this study we have measured lung tissue NAD+ and poly(ADP-ribose) concentrations in response to hyperoxia and niacin deficiency in rats. Male weaning Fischer-344 rats consumed niacin-deficient (ND) or niacin-replete pair-fed (PF) diets for 7 d. Rats from each diet group (n = 6) were then housed in normobaric 85% oxygen for 5 d. Normoxic controls were maintained in air. Hyperoxia increased lung poly(ADP-ribose) concentration by 35% in PF rats, but did not significantly increase levels in ND rats. Niacin deficiency decreased lung NAD+ in normoxic rats, but surprisingly, this deficit was partially reversed by hyperoxia. Liver NAD+ levels increased by 21% during hyperoxia in both diet groups. Heart and kidney NAD+ were unaffected by hyperoxia. Blood was the only tissue measured in which NAD+ was decreased by hyperoxia. Dietary treatment did not affect the increase in the lung wt/b. wt. ratio resulting from hyperoxia. This is the first report in the literature of lung tissue poly(ADP-ribose) measurement. Results show that hyperoxia causes a marked increase in lung poly (ADP-ribose) concentration, but also suggest an adaptation of whole-animal NAD+ metabolism to hyperoxia during niacin deficiency.
 ...
PMID:Lung poly(ADP-ribose) and NAD+ concentrations during hyperoxia and niacin deficiency in the Fischer-344 rat. 872 36