Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.17.3.2 (xanthine oxidase)
 8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interferon-gamma (IFN-gamma) has been reported to up-regulate transcription of the xanthine dehydrogenase (XDH) gene and to regulate XDH and xanthine oxidase (XO) activity in endothelial cells and liver tissue. Macrophages are a source of XDH/XO activity at inflammatory sites and are functionally regulated by IFN-gamma. We studied the effect of IFN-gamma on XDH and XO in rat bone marrow macrophages, rat alveolar macrophages, and murine RAW cells. Instead of an induction of enzyme activity, XDH/XO activity was almost totally lost after incubation with 100 to 1,000 U/ml of IFN-gamma for 24 h in all three cell types. The loss of cell-associated XDH/XO activity was not correlated with the appearance of XDH/XO activity in the media. In addition, the loss of XDH/XO activity could not be accounted for by transcriptional repression, since there was an increase in steady-state levels of XDH mRNA. To determine whether XDH/XO activity might be lost through nitric oxide-mediated inactivation of XDH/XO, we compared the time course and dose response for XDH/XO inactivation with that of nitric oxide production and found them similar. Treatment with the nitric oxide inhibitor N-monomethyl arginine appeared to totally block inactivation of XDH/XO by IFN-gamma. We conclude that upon stimulation with IFN-gamma, inducible nitric oxide in macrophages leads to post-transcriptional inhibition of XDH/XO, possibly minimizing the potential for tissue injury from XO released from macrophages into the inflammatory milieu. Inactivation of XDH may represent yet another "protective" role for nitric oxide at sites of inflammation.
Am J Respir Cell Mol Biol 1994 Nov
PMID:Nitric oxide inactivates xanthine dehydrogenase and xanthine oxidase in interferon-gamma-stimulated macrophages. 752 68

The dynamics and mechanisms of extracellular release of hydrogen peroxide (H2O2) from bovine pulmonary artery endothelial cells (EC) subjected to anoxia, hypoxia, and hypoxia followed by reoxygenation were examined using various inhibitors of enzymatic systems in intact cells and by direct measurement of H2O2 production from isolated EC plasma membranes. Extracellular H2O2 was measured with a fluorometric assay. EC exposed to hypoxia (3% O2) and anoxia (0% O2) released less H2O2 (29.6 +/- 1.3% and 4.2 +/- 0.7%, respectively) compared with EC exposed to normoxia (20% O2). The extracellular release of H2O2 from EC previously exposed to hypoxia for 24 h increased immediately after reoxygenation (20% O2) to 272 +/- 48%, as compared with EC exposed continuously to normoxia (100% release). Inhibition of xanthine oxidase (XO) by allopurinol did not reduce the release of H2O2 from cells exposed to normoxia or hypoxia followed by reoxygenation. Furthermore, inhibitors of cyclooxygenase (indomethacin), phospholipase A2 (quinacrine and chlorpromazine), nitric oxide synthase (L-arginine analogs), the mitochondrial electron transport chain (rotenone and cyanide), and cytochrome P-450 (methoxypsoralen) had no or minimal effect on this release. On the other hand, inhibitors of protein kinase C (calphostin and staurosporine) and NADPH oxidase (diphenyliodonium) reduced the release of H2O2 from EC in a dose-dependent manner in both exposure groups. In separate experiments, plasma membranes isolated from EC were found to produce H2O2 in the presence of NADH or NADPH as electron donors. This was inhibited by diphenyliodonium but not by allopurinol.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1995 Jan
PMID:Release of hydrogen peroxide in response to hypoxia-reoxygenation: role of an NAD(P)H oxidase-like enzyme in endothelial cell plasma membrane. 752 30

Free radicals and other reactive oxygen species (ROS) are important mediators in asbestos-induced lung toxicity. Asbestos fibers are thought to stimulate cells to generate ROS via iron that is present on fibrous silicates. The pathophysiologic responses in the lung after asbestos exposure are characterized by the accumulation of macrophages at the site of fiber deposition and the release of growth factors and proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha). We have examined the role of iron-catalyzed ROS in asbestos induction of TNF-alpha from rat alveolar macrophages. Treatment of alveolar macrophage cultures with asbestos stimulated dose-dependently TNF-alpha secretion, which was inhibited by the addition of deferoxamine, an iron chelator. Asbestos fibers, pretreated with deferoxamine to remove iron from the fibers before addition to alveolar macrophages, also significantly reduced the TNF-alpha response. Consistent with the role of iron on asbestos fibers in catalyzing hydroxyl radical generation, membrane-permeable hydroxyl radical scavengers (tetramethylthiourea, dimethyl sulfoxide) inhibited the asbestos-induced TNF-alpha response. The asbestos-induced increase in TNF-alpha, as well as in interleukin-1 alpha, and their inhibition by tetramethylthiourea occurred at the transcriptional level. The role of ROS in signaling TNF-alpha stimulation was confirmed by use of free radical-generating systems (hypoxanthine-xanthine oxidase, hydrogen peroxide, glucose-glucose oxidase, or ferrous plus hydrogen peroxide). These results suggest that intracellularly generated ROS can stimulate TNF-alpha in alveolar macrophages and that asbestos-induced TNF-alpha gene expression and secretion are mediated by iron-catalyzed product of ROS.
Am J Respir Cell Mol Biol 1995 Jun
PMID:Iron and reactive oxygen species in the asbestos-induced tumor necrosis factor-alpha response from alveolar macrophages. 753 75

Using electron spin resonance (ESR) spin trapping technique, we found that baicalin (B) could scavenge hydroxyl radicals generated from Fenton reaction. It also could scavenge superoxide radicals generated from the reaction system containing xanthine (X) and xanthine oxidase (XO), as was found by using chemiluminescence (CL) method. Kinetic studies on the competition between baicalin and a spin trap 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) in trapping OH showed that baicalin had a kinetic reactive rate constant of the order of 7.7 x 10(11) M-1 s-1 in its reaction with OH, and the studies on the competition between baicalin and ferricytochrome c (f.c.) in trapping O2- gave a kinetic reactive rate constant of 3.2 x 10(6) M-1 s-1 for baicalin in its reaction with O2-. Furthermore, we have investigated the protective effects of baicalin on erythrocyte membranes from hydroxyl free radical injuries. The results showed that baicalin could reduce hydrogen peroxide-induced hemolysis, protect the conformation of sulfhydryl groups (-SH) on membrane proteins and the membrane fluidity of erythrocytes incubated with hydrogen peroxide. The results indicated that baicalin could protect the membranes of erythrocytes from free radical injuries, and it was even more effective than alpha-tocopherol.
Biochem Mol Biol Int 1995 Apr
PMID:Scavenging effects of baicalin on free radicals and its protection on erythrocyte membrane from free radical injury. 754 41

The free radical scavenging effect of "beta catechin", an antioxidant preparation containing green tea extract, ascorbic acid, sunflower seed extract, dunaliella carotene and natural vitamin E, was evaluated. Two techniques were used: electron spin resonance (ESR) spectrometry to measure radical-scavenging activity, and measurement of its effect on iron-induced lipid peroxidation in brain. A 0.05% solution of "beta catechin" completely scavenged 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals (6.1 x 10(15)spins/ml). A 10% solution of "beta catechin" completely scavenged superoxide (4.2 x 10(15) spins/ml) generated by the hypoxanthine-xanthine oxidase system. An undiluted solution of "beta catechin" scavenged about 90% of hydroxyl radicals (3.5 x 10(15) spins/ml) generated by the Fenton reaction. "beta catechin"s effect on the accumulation of thiobarbituric acid-reactive substances (TBARS) was evaluated from tissue obtained from the ipsilateral cortex of FeCl3-induced epileptic rats. Oral administration of "beta catechin" (1 or 2ml/kg body weight) both inhibited TBARS formation and increased the activity of superoxide dismutase (SOD) in the ipsilateral cortex 30 min after iron-salt injection into the left sensory motor cortex. These data suggest that "beta catechin" has an antioxidant effect and may have a prophylactic effect against aging and other neurological diseases related to free radical mechanisms.
Biochem Mol Biol Int 1995 Apr
PMID:Antioxidant effects of "beta catechin". 754 42

Superoxide radical (O2-.), generated by the xanthine-xanthine oxidase system, induces significant amount (20%) of single-strand breaks in plasmid pBR322 DNA. This is almost completely inhibited by its specific scavenger, superoxide dismutase. The biological antioxidants, at near physiological concentrations show great variation in their modulation of DNA damage induced by O2-.. The thiols glutathione, cysteine and dithiothreitol do not protect DNA, instead they greatly enhance the strand-breaking activity of this free radical. However, the lipid soluble antioxidants tannic acid, butein, canthaxanthin, beta-carotene and lipoate offered significant protection to plasmid DNA against O2-.. Since O2-. is the most abundant reactive oxygen species generated, the above mentioned modulating abilities of biological antioxidants may have significant biological implications.
Biochem Mol Biol Int 1995 Feb
PMID:Variation in the modulation of superoxide-induced single-strand breaks in plasmid pBR322 DNA by biological antioxidants. 766 83

ESR spin trapping was utilized to study the singlet oxygen (1O2) generation in the reaction of superoxide (O2) with H2O2. The spin trap used was 2,2,6,6-tetramethyl-4-piperdone. Incubation of xanthine, xanthine oxidase and H2O2 generated 1O2 spin adduct signal. Omission of xanthine, xanthine oxidase or H2O2 caused a sharp decrease in 1O2 generation. 1O2 scavenger, sodium azide, inhibited 1O2 generation while .OH scavenger, ethanol, only slightly decreased the signal intensity. Potassium superoxide (KO2) decomposition generated 1O2. Catalase and sodium azide inhibited 1O2 generation and H2O2 enhanced it. The results demonstrate that O2 is capable of generating 1O2 upon reaction with H2O2.
Biochem Mol Biol Int 1995 May
PMID:Singlet oxygen generation in the superoxide reaction. 766 19

The aim of the research was to study the role played by extracellular O2-radicals, which are implicated in cardiac cell damage and the protective effect by cell-permeable, nitroxide, superoxide dismutase-mimics. Cardiomyocytes cultures from 1-day-old rats served as the test-system. Experiments were performed since 5th day in culture when > 80% of the cells were beating myocardial cells. Oxidative damage was induced by 0.5 mM hypoxanthine and 0.06 U/ml xanthine oxidase or by 10 mM glucose and 0.15 U/ml glucose oxidase. The parameters used to evaluate damages were spontaneous beating, lactate dehydrogenase release and ATP level. The rhythmic pulsation was followed microscopically. To determine the kinetics of cytosolic enzyme release from the cells, media samples were collected at various points of time and assayed for enzyme activity. To determine the cellular ATP, cells were washed with sodium phosphate buffer, scraped off and boiled for 3 min with sodium phosphate buffer. Following centrifugation the supernatant was collected and ATP was determined by the chemiluminogenic assay using firefly tails. The present results indicate that nitroxide stable free radicals in the millimolar concentration range, provide full protection without toxic side-effect. Unlike exogenously added SOD that failed to protect, exogenous catalase provided almost full protection. In addition, the metal-chelating agent dipyridyl, but not diethylene-triamine-pentaacetate or desferrioxamine, protected the cultured cells. The present results suggest that H2O2 is the predominant toxic species mediating the oxidative damage whereas extracellular superoxide radical does not contribute to cultured cardiomyocyte damage.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Biochem 1995 Apr 26
PMID:Do nitroxides protect cardiomyocytes from hydrogen peroxide or superoxide? 767 30

Acute inflammatory lung injury often complicates hemorrhagic shock, a systemic ischemia-reperfusion syndrome. Because oxygen radicals are generated during ischemia-reperfusion, and oxygen radicals can activate nuclear regulatory factors that affect transcription of proinflammatory cytokines, we examined the premise that oxygen radicals increase interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) expression in lung mononuclear cells after hemorrhage. Intraparenchymal pulmonary mononuclear cells isolated 1 h after hemorrhage from control mice had increased levels of mRNA for IL-1 beta (P < 0.001) and TNF-alpha (P < 0.05) compared with cells from sham-hemorrhaged mice. Hemorrhaged mice treated with the oxygen radical scavenger dimethylthiourea (DMTU) had decreased levels of mRNA for IL-1 beta in pulmonary mononuclear cells, compared with hemorrhaged controls (P < 0.05). In hemorrhaged mice depleted of xanthine oxidase (XO) by a tungsten-enriched diet, pulmonary mononuclear cell mRNA levels for IL-1 beta and TNF-alpha were significantly decreased (P < 0.01 and 0.05, respectively), compared with cells from hemorrhaged control mice fed a normal diet. Similarly, mRNA transcripts for IL-1 beta and TNF-alpha among pulmonary mononuclear cells from hemorrhaged mice treated with allopurinol, an inhibitor of XO, were also significantly reduced (P < 0.05 and 0.001, respectively), compared with hemorrhaged control mice not treated with allopurinol. Our results indicate that XO-derived oxygen radicals contribute to the increased expression of mRNA for IL-1 beta and TNF-alpha, which occurs among pulmonary mononuclear cell populations immediately after hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1995 Apr
PMID:Xanthine oxidase-derived oxygen radicals increase lung cytokine expression in mice subjected to hemorrhagic shock. 769 23

It has been documented that cytokines can induce the formation of reactive oxygen species (ROS) in the liver, and that an inflammatory reaction can locally increase the production of ROS, but it remains unknown whether in vivo a subcutaneous (s.c.) inflammatory reaction can induce the formation of ROS in the liver. To determine in vivo whether an inflammatory reaction, able to decrease the amount of hepatic cytochrome P450, enhances the presence of ROS in the liver, turpentine was injected s.c. to rabbits, which were sacrificed 48 hours later. Control rabbits received saline s.c. The amount and activity of cytochrome P450, as well as several parameters reflecting the presence of ROS were assessed in the liver. Total amount of cytochrome P450 was reduced, as was its activity, assessed by the rates of hydroxylation of aniline and of demethylation of aminopyrine. Moreover, lipid peroxidation increased, while the activity of the enzymatic scavengers, i.e. catalase, glutathione peroxidase and superoxide dismutase decreased. In addition, hepatic concentrations of reduced glutathione were diminished. On the other hand, the activity of the xanthine oxidase system was enhanced by almost 200%. These results strongly suggest an increased presence of ROS. The changes in the amount of cytochrome P450 were inversely correlated with lipid peroxidation. In conclusion, these results show that in vivo an inflammatory reaction, that reduces total cytochrome P450 and its activity, produces simultaneously an oxidative stress in the liver.
Res Commun Mol Pathol Pharmacol 1995 Feb
PMID:Inflammation-induced decrease in hepatic cytochrome P450 in conscious rabbits is accompanied by an increase in hepatic oxidative stress. 774 59


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>