Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have shown that susceptibilities of hepatocytes and endothelial cells to H2O(2)-induced injury are altered by changes in the intracellular activity of Cu,Zn-containing superoxide dismutase (CuZn-SOD). To evaluate the role of intracellular CuZn-SOD in oxidant-induced injury to rat cardiac myocytes, cells with reduced CuZn-SOD activity but normal ATP content were either isolated from the hearts of adult copper-deficient rats or obtained by treatment of normal isolated adult myocytes with diethyldithiocarbamate. These myocytes and controls with normal CuZn-SOD activity were exposed to either reagent H2O2 or oxidants generated by extracellular glucose oxidase plus glucose or xanthine oxidase plus xanthine. It was shown that myocytes with CuZn-SOD activities reduced by 70-90% were equally susceptible to H2O2 and the two oxidant-generating systems as the control myocytes. The findings suggest that in adult cardiac myocytes, in contrast to the situation in some other cells, intracellular CuZn-SOD may not have a significant defensive role against acute H2O(2)-induced injury. The possibility remains, however, that changes in the activity of this enzyme, e.g., in copper deficiency, may be relevant to the ability of myocytes to cope with chronic oxidative stress resulting from imbalance between intracellular oxygen radical-generating and -scavenging systems.
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PMID:Role of intracellular SOD in oxidant-induced injury to normal and copper-deficient cardiac myocytes. 790 Aug 65

The present investigation deals with the in vivo effects of oxygen free radicals (OFRs) in the absence and presence of scavengers of OFRs (superoxide dismutase, SOD, and catalase) on the cardiac function and contractility and with the in vitro effects of exogenous OFRs and various pH and pO2 on the release of acid hydrolases from dog myocardial lysosomes. The hemodynamic measurements were made before and at various intervals after administration of OFRs for up to 2 h. Xanthine plus xanthine oxidase (X-XO) and opsonized zymosan were used to generate OFRs. Oxygen free radicals produced a decrease in the cardiac function and indices of myocardial contractility. SOD alone or in combination with catalase tended to protect the cardiac function against the deleterious effects of OFRs. There was about a threefold increase in the release of cathepsin D activity in vitro from the lysosomes in the preparations treated with X-XO as compared to those without such treatment. The presence of SOD prevented the release of cathepsin D from the lysosomes. The changes in pH (4.5, 5.5, 6.0, 6.5, 7.4, 8.0) alone did not cause any increase in the enzyme release. However, the presence of OFRs at each pH resulted in a similar increase (about threefold) in the release of cathepsin D. Similarly the changes in pO2 alone did not cause the release of cathepsin D, but there were marked increases in the release of cathepsin D at each pO2 in the presence of OFRs. These data indicate that it is the oxygen free radicals and not the alterations in pH or pO2 that are primarily responsible for the release of lysosomal hydrolases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxygen free radicals and cardiac depression. 792 55

The implication of eicosanoid metabolism and its relationship with oxygen free radical production in the process of ischemia-reperfusion associated with rat pancreas transplantation has been explored in this study. For this purpose male Sprague-Dawley rats were classified as follows: group I, control animals not surgically manipulated; group II, pancreas transplantation, after 30 min preservation in UW solution; group III, pancreas transplantation after 12 h preservation under the same conditions; group IV, same as group III but with administration of SOD 5 min prior to organ revascularization. The results show post-transplantation increases in 6-keto-PGF1 alpha, TXB2, LTB4 and 12-HETE in pancreatic tissue independent of preservation time. The fact that SOD administration could reverse these increases even though an efficient xanthine oxidase irreversible inhibitor such as allopurinol was present in the preservation solution suggests that eicosanoid generation in the recipient rat would be mediated by an oxygen free radical dependent mechanism not exclusively dependent on endothelial xanthine oxidase activity.
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PMID:Arachidonate metabolism in ischemia-reperfusion associated with pancreas transplantation. 801 60

Aortic rings, 4 mm in length, were obtained from rats and placed on isometric force transducers in oxygenated Krebs buffer. Following a period of stabilization, the cumulative dose response relationship to norepinephrine was assessed. The vessels were washed and allowed to return to baseline in Krebs buffer containing xanthine (0.5 mM). Xanthine oxidase (0.1 U/ml) was then added to the bath and vessels incubated for 30 min. The vessels were resuspended in Krebs buffer and cumulative dose-response curves to norepinephrine reevaluated. The results indicate that generation of reactive oxygen metabolites by xanthine/xanthine oxidase decreases the pD2 from 7.80 +/- 0.04 to 7.40 +/- 0.09 with the endothelium intact. Removal of the endothelium did not attenuate the contractile dysfunction, indicating that endothelial-derived metabolites were not mediating the loss of vasoconstrictor effectiveness. Maximal tension development did not differ between normal and oxidized vessel rings. Introduction of oxypurinol (0.2 mg/ml) to the bath prevented the loss of constrictor responsiveness, thereby confirming that all of the oxidants were derived from the xanthine/xanthine oxidase reaction. Superoxide dismutase (200 U/ml) partially prevented the loss of norepinephrine responsiveness produced by xanthine oxidase-derived radicals. The pD2 in the SOD + xanthine/xanthine oxidase-treated vessels rings (7.19 +/- 0.11) was significantly lower than control vessel rings (7.49 +/- 0.04) and significantly higher than xanthine/xanthine oxidase-treated vessels (6.89 +/- 0.06). Catalase (1000 U/ml) also partially attenuated the loss of vascular norepinephrine responsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of reactive oxygen metabolites on norepinephrine-induced vasoconstriction. 807 Jun 89

A housekeeping basolateral Cl- channel of rabbit gastric parietal cells, the single channel conductance of which is about 0.3 picosiemens, is opened by prostaglandin E2 and closed by intracellular application of guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S). In the present patch clamp study, we found a novel GTP gamma S-dependent regulatory mechanism of the Cl- channel. GTP gamma S significantly decreased the open probability of the single Cl- channel without altering unit conductance. An intracellular application of superoxide dismutase (SOD; 100 units/ml) inhibited the GTP gamma S (50 microM)-induced closure of the Cl- channel. SOD plus catalase (100 units/ml) also inhibited the GTP gamma S-induced effect, while catalase alone did not inhibit it. In the absence of GTP gamma S, an intracellular application of hydrogen peroxide (H2O2; 30 microM) did not affect the Cl- channel current. Desferrioxamine (50 microM) which inhibits hydroxyl radical (.OH) production was without effect on the GTP gamma S-induced closure. These results suggest that the GTP gamma S-induced closure of the Cl- channel was due to intracellular production of superoxide (O2.-), but not due to .OH or H2O2. Furthermore, an artificial production of O2.- inside the cell by lumazine (50-100 microM) plus xanthine oxidase (0.5-1 milliunit/ml) in the absence of GTP gamma S also closed the channel. The lumazine/xanthine oxidase-induced closure of the channel was inhibited by SOD, but not by catalase or desferrioxamine. We conclude from these results that GTP-binding protein-coupled production of O2.- leads to closure of the Cl- channel in rabbit gastric parietal cells.
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PMID:A GTP-binding protein inhibits a gastric housekeeping chloride channel via intracellular production of superoxide. 808 7

One of the current theories of cardiovascular disease is that it may begin with oxygen radical-induced damages. Extensive studies have been made in different laboratories to elucidate the mechanism of oxidative damages in the presence of added iron salts. However, those in vitro studies are unlikely to be relevant to the in vivo situation, where in the normal physiological condition most of the iron remains bound with proteins. In the present study we have demonstrated that an in vitro system containing desferrioxamine, a strong iron chelator, superoxide generated by the action of xanthine oxidase on acetaldehyde initiates lipid peroxidation and protein changes in the guinea pig cardiac microsomes. We have further demonstrated that superoxide-initiated lipid peroxidation and protein changes are completely prevented by ascorbic acid. SOD also prevents but catalase, alpha-tocopherol, glutathione, uric acid, thiourea, mannitol and histidine are without effect. When NADPH is used instead of generated superoxide, the lipid peroxidation and protein changes are exclusively inhibited by ascorbic acid. SOD, catalase and other antioxidants are ineffective. The results obtained with guinea pigs may be extrapolated to humans, because like guinea pigs humans are also incapable of synthesizing ascorbic acid.
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PMID:Protective effect of ascorbic acid against lipid peroxidation and oxidative damage in cardiac microsomes. 810 91

To determine the effect of oxidative stress on expression of extracellular superoxide dismutase (EC-SOD), CuZn-SOD and Mn-SOD, two fibroblast lines were exposed for periods of up to 4 days to a wide concentration range of oxidizing agents: xanthine oxidase plus hypoxanthine, paraquat, pyrogallol, alpha-naphthoflavone, hydroquinone, catechol, Fe2+ ions, Cu2+ ions, buthionine sulphoximine, diethylmaleate, t-butyl hydroperoxide, cumene hydroperoxide, selenite, citiolone and high oxygen partial pressure. The cell lines were cultured both under serum starvation and at a serum concentration that permitted growth. Under no condition was there any evidence of EC-SOD induction. Instead, the agents uniformly, dose-dependently and continuously reduced EC-SOD expression. We interpret the effect to be due to toxicity. Enhancement of the protection against oxidative stress by addition of CuZn-SOD, catalase and low concentrations of selenite did not influence the expression of any of the SOD isoenzymes. Removal of EC-SOD from cell surfaces by heparin also did not influence SOD expression. Mn-SOD was moderately induced by high doses of the first 11 oxidants. Apart from reduction at high toxic doses, there were no significant effects on the CuZn-SOD activity by any of the treatments. Thus EC-SOD, previously shown to be profoundly influenced by inflammatory cytokines, was not induced by its substrate or other oxidants. In a similar fashion, Mn-SOD, previously shown to be greatly induced and depressed by cytokines, was only moderately influenced by oxidants. We suggest that the regulation of these SOD isoenzymes in mammalian tissues primarily occurs in a manner co-ordinated by cytokines, rather than as a response of individual cells to oxidants.
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PMID:Effects of oxidative stress on expression of extracellular superoxide dismutase, CuZn-superoxide dismutase and Mn-superoxide dismutase in human dermal fibroblasts. 813 41

We determined activities of adenosine deaminase (ADA), 5' nucleotidase (5NT), xanthine oxidase (XO), superoxide dismutase (Cu-Zn SOD), and catalase (CAT) enzymes in 15 human laryngeal tissues with well-differentiated squamous cell carcinomas, in 15 corresponding tumor-free adjacent tissues and in 7 normal laryngeal tissues. We found lower ADA and 5NT and higher XO, Cu-Zn SOD, and CAT activities in cancerous tissues than those in corresponding noncancerous ones. In the correlation analysis, we established one positive intercorrelation, which was between ADA activities of tumor tissues and noncancerous adjacent tissues. We also found some significant intracorrelations between enzyme activities of the tissues, all of which were positive in cancerous ones.
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PMID:Adenosine deaminase, 5' nucleotidase, xanthine oxidase, superoxide dismutase, and catalase activities in cancerous and noncancerous human laryngeal tissues. 813 95

Adenosine deaminase (ADA), 5'-Nucleotidase (5NT), Xanthine oxidase (XO), Cu-Zn Superoxide dismutase (SOD) and Catalase (CAT) activities were determined in gastric juices from patients with gastric cancer, ulcer, gastritis and from healthy subjects. Enzyme activities were given as units per ml gastric juice and units per mg protein in gastric juice. ADA, 5NT and XO activities were found lower and protein concentrations were found higher in the cancer group than controls. There was however no significant difference between Cu-Zn SOD activities of the cancer and control groups. In all groups including control one, we could not find catalase activities in most of the samples. On the other hand, ADA, 5NT activities and protein concentrations in the gastric juice were lower in the gastritis group than control group. In the ulcer group, we found higher Cu-Zn SOD and XO activities and lower 5NT activity and protein concentrations compared with control values. In an attempt to establish statistical correlations between mean enzyme activities, pH and protein concentrations in the gastric juices of the groups, we found noticeable intra and inter-correlations, which indicated possible relations between DNA and free radical metabolizing enzymes.
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PMID:Adenosine deaminase, 5'-nucleotidase, xanthine oxidase, superoxide dismutase, and catalase activities in gastric juices from patients with gastric cancer, ulcer, and atrophic gastritis. 814 35

We quantitated the ability of intratracheally administered liposome-encapsulated antioxidant enzymes to reduce reactive oxygen species injury to the pulmonary microvasculature. Cationic liposomes containing 3,500 U of Cu,Zn superoxide dismutase (Cu,Zn SOD) and 3,124 U of catalase were instilled into rabbits. The animals were killed 2-72 h later and their lungs were removed and perfused with Krebs Ringer with 5% wt/vol of fat-free bovine serum albumin. The pulmonary filtration co-efficient (Kf,c) was measured before and after adding 500 microM xanthine and 5 mU/ml xanthine oxidase (XO) into the lung perfusate. Two hours after a single intratracheal instillation of liposome-entrapped Cu,Zn SOD and catalase, lung antioxidant enzyme activities were 34 and 125% higher than the corresponding control values, remained virtually unchanged for up to 8 h post-instillation, and then decreased, reaching baseline values between 24 and 72 h. Addition of xanthine and XO into the lung perfusate of un-instilled rabbits, or rabbits that received liposomes with inactivated enzymes, caused a 100% increase in Kf,c (control value: 2 +/- 0.12 ml.min-1 x cmH2O-1 per 100 g dry lung weight). On the other hand, Kf,c values of rabbits lungs instilled with liposome-encapsulated active Cu,Zn SOD and catalase and challenged with xanthine and XO 8-24 h later remained at baseline levels. Instillation of liposomes containing either enzyme was equally effective in preventing the increase in Kf,c, indicating that both superoxide anions and hydrogen peroxide were necessary for the initiation of injury. We concluded that intratracheal instillation of liposome-encapsulated antioxidant enzymes caused a transient increase of lung antioxidant enzyme levels which protects the pulmonary microvasculature from free radical-initiated injury.
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PMID:Mitigation of oxidant injury to lung microvasculature by intratracheal instillation of antioxidant enzymes. 823 68


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