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)

The effects of prolonged intravenous administration of bovine milk xanthine oxidase (EC 1.2.3.2.) on blood lipids and arterial integrity were measured to determine if the administration of this enzyme produces metabolic changes conducive to plaque formation. New Zealand White rabbits were injected intravenously with bovine milk xanthine oxidase at 4-day intervals during a 13-week test period. At the end of the test period, the rabbits were killed and blood, heart, aorta, liver, and kidneys were collected and evaluated. Rabbits injected with phosphate buffer or acid-denatured xanthine oxidase for the same length of time served as negative controls. Additional rabbits fed a diet containing 3% added cholesterol for the same time period served as positive controls. The administration of xanthine oxidase in large amounts over a prolonged period did not alter serum cholesterol or triglyceride levels and did not reduce plasmalogen levels in the aorta or heart. Xanthine oxidase administration did not induce arterial plaque formation. Cholesterol feeding over the same time period increased serum cholesterol levels, reduced liver xanthine oxidase activity levels and resulted in a marked development of arterial plaques. Althouth xanthine oxidase activity was found in liver from all rabbits, enzyme activity was not detectable in aorta, heart or kidneys from any rabbit. Free or complexed bovine milk xanthine oxidase could not be demonstrated in heart, aorta, liver or kidneys from any of the rabbits with immunodiffusion or with immunofluorescent techniques. The study showed that when large intravenous doses of bovine milk xanthine oxidase were given to rabbits, the enzyme was not deposited in heart, aorta, liver or kidneys. The study also showed that large intravenous doses of xanthine oxidase over prolonged periods did not deplete arterial or coronary tissue plasmalogens, and did not induce arterial plaque formation.
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PMID:Bovine milk xanthine oxidase, blood lipids and coronary plaques in rabbits. 87 Jun 48

Routine culture of endothelial cells currently includes the use of heparin, which significantly reduces cell doubling time and increases cell population size. Heparin protects cultured arterial endothelial cells from damage by toxic oxygen metabolites produced by the action of xanthine and xanthine oxidase. Because of our hypothesis implicating free radicals in cell injury caused by Rickettsia rickettsii, we have carried out a series of experiments to examine the effects of heparin on injury to endothelial cells infected by this microorganism. These studies showed that heparin does not inhibit replication of R. rickettsii in the cytoplasm of endothelial cells. Furthermore, heparin appears to exhibit a protective effect on the infected host cell as measured by (i) reduced plaque size, (ii) increased longevity of the cell monolayer, (iii) reduction in the amount of lactic dehydrogenase released from infected cells, and (iv) reduction in the levels of intracellular peroxides formed in infected cells. Electron microscopic studies also show a significant reduction in dilatation of the rough-surfaced endoplasmic reticulum of the infected cells in the presence of heparin. These observations appear to lend additional support to involvement of an oxidative mechanism in human endothelial cell injury caused by R. rickettsii.
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PMID:Heparin protects human endothelial cells infected by Rickettsia rickettsii. 193 10

Studies on the mechanism of immunosuppression shown by adenine comprised two areas: (1) Toxicity studies on hepatic, muscle and renal tissues were undertaken to ascertain if immunosuppression was a result of a non specific toxicity. (2) Studies to determine whether immunosuppression is a function of the inhibitory effect on de novo and salvage pathways of purine nucleotide metabolism. Toxicity studies in mice indicated that adenine caused an acute, reversible renal tubular necrosis and that allopurinol, when combined with adenine, could abrogate both the renal toxicity and immunosuppressive activity of the purine base. This result indicated that the toxic and/or immunosuppressive compound may be a xanthine oxidase catalysed product of adenine. Further studies indicated that it was unlikely that a major part of the immunosuppressive activity of adenine was due to the renal toxicity exerted by this compound. Splenic PRPP levels were found to peak on day 4 after antigen administration (day 0) and this corresponded with the peak in antibody plaque response which occurred at day 4 to 5. Adenine given at an immunosuppressive dose of 25 mumoles/mouse on day 0, 1 resulted in a significant inhibition of splenic PRPP levels on day 2 of the response. This effect on splenic PRPP levels on day 2 was also found with hypoxanthine given at an immune enhancing dose and therefore would indicate that depression of splenic PRPP per se is not responsible for the immunosuppression. Adenosine given at immunosuppressive doses was found not to affect PRPP levels in the spleen and hepatic PRPP levels were unaffected by adenine, adenosine and hypoxanthine. The in vivo effects of adenine on hypoxanthine-guanine phosphoribosyltransferase showed that adenine could inhibit significantly this salvage pathway in spleen and liver and that this inhibition could be overcome with concomitant administration of allopurinol. A metabolite of adenine which could contribute to its immunosuppressive activity may be 2-hydroxyadenine since it is derived from the xanthine oxidase catalysed oxidation of adenine inhibited hypoxanthine-guanine phosphoribosyltransferase gave similar renal toxicity to adenine and was immunosuppressive.
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PMID:Studies on the mechanism of immunosuppression with adenine. 241 71

The effect of an antigenic challenge with sheep red blood cells (SRBC) on the activities of cytochrome P-450-dependent and -independent xenobiotic metabolizing enzymes and on lipid peroxidation in the liver was investigated. The studies were carried out using three mouse strains of C57B1/10 and three strains of C3H backgrounds which are cogenic, differing genetically at the H-2 complex. The basal levels of aryl hydrocarbon hydroxylase (AHH) and 7-ethoxycoumarin O-deethylase (7-Ec) were different among congenic strains. The activity of 7-Ec was lower in C3H background mice than in B10 background mice. Similarly, the difference due to the strain and the H-2 locus was detected in the activities of P-450-independent enzymes such as malathion and diethyl succinate carboxylesterases, glutathione S-transferase, and epoxide hydrolases in microsomal and cytosolic fractions. The degree of immune responsiveness in these mice was determined by a plaque forming cell assay. Within the same background, the H-2b mouse strain was a high responder and the H-2k a low responder to SRBC. However, treatment with SRBC had no significant depressive effect on P-450-dependent enzyme activities except in C3H/He. Activity of AHH was suppressed in C3H/He mice. Treatment with SRBC had no effect on P-450-independent enzyme activities except for malathion carboxylesterase: the activity was increased in C3H/He and C3H.JK, whereas it was decreased in B10. The basal level of lipid peroxidation was lower in C3H/He and C3H.JK. The treatment produced a significant enhancement in lipid peroxidation in C3H/He, B10 and B10.BR (P less than 0.05) with a concomitant increase in xanthine oxidase activity (P less than 0.05). Thus, the present study revealed that a specific antigenic challenge, unlike non-specific immunostimulants (e.g. poly IC, endotoxin), does not necessarily inhibit P-450-dependent xenobiotic metabolizing enzymes even though antigen challenge increased XO activity and lipid peroxidation. The possible roles of an increase in lipid peroxidation and xanthine oxidase activity in immune response to SRBC and xenobiotic metabolizing enzymes are discussed.
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PMID:Effect of induction of T-cell-dependent antibody with sheep red blood cells on P-450-dependent and -independent xenobiotic metabolizing enzymes. 348 42

Urokinase-type plasminogen activator (uPA) and its cell surface receptor (uPAR) have been shown to be expressed in macrophages in atherosclerotic arterial walls, but the regulatory mechanisms of their expression remain unclear. The present study was performed to examine the effects of lysophosphatidylcholine (lysoPC), an important atherogenic lipid, on the expression of uPA and uPAR in human monocyte-derived macrophages. LysoPC upregulated the mRNA expression of uPA and uPAR, and it increased the protein expression of uPA in the culture medium and bound to the cell surface and of uPAR in the particulate fraction of the cells. LysoPC significantly increased the binding of the amino-terminal fragment of uPA to the treated cells and the cell-associated plasminogen activator activity. LysoPC stimulated superoxide anion production and increased intracellular oxidant levels in the cells. The combined incubation with reduced glutathione diethyl ester or N-acetylcysteine, antioxidants, suppressed the upregulation of uPA and uPAR mRNA and the increase in plasminogen activator activity by lysoPC. uPA and uPAR mRNA expression was also induced by the incubation with xanthine and xanthine oxidase, a superoxide anion-generating system. The results suggest that lysoPC increased the expression of uPA and uPAR and their functional activities in human monocyte-derived macrophages, at least in part through a redox-sensitive mechanism. This coordinate increase in the expression of uPA and uPAR in human macrophages by lysoPC could play an important role in plaque formation and disruption, arterial remodeling, and angiogenesis in atherosclerotic arterial walls.
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PMID:Lysophosphatidylcholine induces urokinase-type plasminogen activator and its receptor in human macrophages partly through redox-sensitive pathway. 1063 25

Oxidative stress may regulate cellular function in multiple pathological conditions, including atherosclerosis. One feature of the atherosclerotic plaque is calcium mineral deposition, which appears to result from the differentiation of vascular osteoblastic cells, calcifying vascular cells (CVC). To determine the role of oxidative stress in regulating the activity of CVC, we treated these cells with hydrogen peroxide (H(2)O(2)) or xanthine/xanthine oxidase (XXO) and assessed their effects on intracellular oxidative stress, differentiation, and mineralization. These agents increased intracellular oxidative stress as determined by 2,7 dichlorofluorescein fluorescence, and enhanced osteoblastic differentiation of vascular cells, based on alkaline phosphatase activity and mineralization. In contrast, H(2)O(2) and XXO resulted in inhibition of differentiation markers in bone osteoblastic cells, MC3T3-E1, and marrow stromal cells, M2-10B4, while increasing oxidative stress. In addition, minimally oxidized low-density lipoprotein (MM-LDL), previously shown to enhance vascular cell and inhibit bone cell differentiation, also increased intracellular oxidative stress in the three cell types. These effects of XXO and MM-LDL were counteracted by the antioxidants Trolox and pyrrolidinedithiocarbamate. These results suggest that oxidative stress modulates differentiation of vascular and bone cells oppositely, which may explain the parallel buildup and loss of calcification, seen in vascular calcification and osteoporosis, respectively.
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PMID:Oxidative stress modulates osteoblastic differentiation of vascular and bone cells. 1149 84

Recurrent herpes labialis (RHL) occurs in up to 40% of the population. Although the disease is usually self-limiting, patients seek treatment because of the significant pain and visibility of the lesion. Xanthine oxidase inhibitors (XOI) have been reported to have a potent antiviral effect against influenza-A virus. We examined the effect of the systemic xanthine oxidase inhibitor, allopurinol, on RHL duration of illness, severity of symptoms, number and frequency of recurrence during a 4-year follow up period in Egyptian patients. Duration of illness was shortened by about 25%, early disappearance of pain and other symptoms occurred. Also, aborted episodes were noticed when allopurinol was given just after beginning of common colds, at the prodromal stage of RHL or during severe stress conditions. Patients receiving 3 courses of treatment had markedly decreased recurrences during the follow up period. Ex vivo experiments to examine virus-induced plaque formation on Vero cells in the absence or presence of different concentrations of the drug could not prove any direct anti herpetic effect of the drug. However, allopurinol seems to be safe and effective in reducing duration of RHL and to abort lesion or prevent its appearance in treated patients even when they experience immunosuppressive conditions.
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PMID:Allopurinol as a potential therapeutic agent for recurrent herpes labialis. 1296 36

Although hypertension is a major risk factor for atherosclerosis, its underlying mechanisms remain to be delineated. We have recently reported that both endothelin-1 (ET-1) and vascular cellular adhesion molecule-1 (VCAM-1) levels, key early markers of atherosclerosis, are significantly elevated in carotid arteries of deoxycorticosterone acetate (DOCA)-salt hypertensive rats, a model known for its suppressed plasma renin levels. This study tested the hypothesis that ET-1 augments arterial VCAM-1 expression through NADPH oxidase-derived superoxide (O2-). Carotid arteries of DOCA-salt or sham-operated rats were transduced ex vivo with extracellular superoxide dismutase (EC-SOD), dominant negative HA-tagged N17Rac1 that inhibits Rac1, the small GTPase component of NADPH oxidase, or beta-galactosidase (beta-gal) reporter gene (5x10(10) plaque formation units [pfu]/mL), and the effect of transgene expression on O2- and VCAM-1 levels was assayed 24 hours afterward. The arterial activity of NADPH oxidase but not xanthine oxidase was significantly higher in DOCA-salt than in sham rats, which was abolished by the selective ETA receptor antagonist ABT-627 (3x10(-8) mol/L), NADPH oxidase inhibitor apocynin (10(-4) mol/L), or dominant negative Rac1 gene transfer. The levels of O2- and VCAM-1 were significantly increased in arteries of DOCA-salt rats, an effect that was ameliorated after EC-SOD or dominant negative Rac1 but not beta-gal reporter gene transfer. ABT-627 and apocynin also significantly reduced elevated VCAM-1 levels in ET-1-treated arteries of normal rats and arteries of DOCA-salt rats. The results of this study indicate that ET-1 stimulates arterial VCAM-1 expression by producing O2- from an ETA receptor/NADPH oxidase pathway in low-renin mineralocorticoid hypertension.
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PMID:Endothelin-1 stimulates arterial VCAM-1 expression via NADPH oxidase-derived superoxide in mineralocorticoid hypertension. 1451 26

The prevalence of diabetes mellitus is rising worldwide and has reached epidemic dimensions. Diabetes mellitus places patients at high cardiovascular risk. High blood glucose levels, altered insulin signaling, reactive oxygen species (ROS), inflammation, and protein kinase C activation might lead to a decrease in nitric oxide (NO) bioavailability. Diminished NO and enhanced oxidative stress play a central role in several pathophysiologic pathways, leading to vascular damage, such as endothelial dysfunction, vascular inflammation, atherosclerotic plaque formation and vulnerability, and promotion of a prothrombotic state. Possible sources of oxidative excess in diabetes are reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, xanthine oxidase, uncoupled NO synthase, and the mitochondria. Advances in understanding the pathophysiologic mechanisms leading to vascular damage in diabetes will result in discovery of new therapeutic targets, which should help reduce cardiovascular risk in these patients.
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PMID:Nitric oxide, oxidative excess, and vascular complications of diabetes mellitus. 1501 9

The goal of the present study was to investigate the antifibrotic role of inducible nitric oxide synthase (iNOS) in Peyronie's disease (PD) by determining whether a plasmid expressing iNOS (piNOS) injected into a PD-like plaque can induce regression of the plaque. A PD-like plaque was induced with fibrin in the penile tunica albuginea of mice and then injected with a luciferase-expressing plasmid (pLuc), either alone or with piNOS, following luciferase expression in vivo by bioluminescence imaging. Rats were treated with either piNOS, an empty control plasmid (pC), or saline. Other groups were treated with pC or piNOS, in the absence of fibrin. Tissue sections were stained for collagen, transforming growth factor (TGF) beta1, and plasminogen-activator inhibitor (PAI-1) as profibrotic factors; copper-zinc superoxide dismutase (CuZn SOD) as scavenger of reactive oxygen species (ROS); and nitrotyrosine to detect nitric oxide reaction with ROS. Quantitative image analysis was applied. Both iNOS and xanthine oxido-reductase (XOR; oxidative stress) were estimated by Western blot analysis. Luciferase reporter expression was restricted to the penis, peaked at 3 days after injection, but continued for at least 3 wk. In rats receiving piNOS, iNOS expression also peaked at 3 days, but expression decreased at the end of treatment, when a considerable reduction of plaque size occurred. Protein nitrotyrosine, XOR, and CuZn SOD increased, and TGFbeta1 and PAI-1 decreased. The piNOS gene transfer regressed the PD plaque and expression of profibrotic factors, supporting the view that endogenous iNOS induction in PD is defense mechanism by the tissue against fibrosis.
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PMID:Gene transfer of inducible nitric oxide synthase complementary DNA regresses the fibrotic plaque in an animal model of Peyronie's disease. 1524 Apr 26


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