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)

To evaluate the regulation of endothelial cell Cu,Zn-SOD, we have exposed bovine pulmonary artery endothelial cells in culture to hyperoxia and hypoxia, second messengers or related agonists, hormones, free radical generating systems, endotoxin, and cytokines and have measured Cu,Zn-SOD protein of these cells by an ELISA developed in our laboratory. Control preconfluent and confluent cells in room air contained 196 +/- 18 ng Cu,Zn-SOD/10(6) cells. A23187 (0.33 microM), forskolin (10 microM), isobutylmethylxanthine (0.1 mM), dexamethasone (1 microM), triiodothyronine (1 microM) and retinoic acid (1 microM) failed to alter this level of Cu,Zn-SOD. Exposure to anoxia and hyperoxia both elevated the level approximately 1.5-2.0-fold over 20% oxygen-exposed controls at 48-72 hr. Similarly, exposures to glucose oxidase (0.0075 units/ml), menadione (12.5 microM), xanthine-xanthine oxidase (10 microM, 0.03 units/ml) and H2O2 (0.0005%) increased the level up to two-threefold over controls at 24-48 hr. Lipopolysaccharide, TGF beta 1, TNF alpha, and Il-1 also increased levels of cellular Cu,Zn-SOD, but only in proliferating cells. Il-2, Il-4, interferon-gamma, and GM-CSF had no effect on Cu,Zn-SOD. All treatments that elevated SOD resulted in inhibition of cellular growth, but decreased growth of cells at confluence alone was not associated with increased Cu,Zn-SOD. We propose from these studies that Cu,Zn-SOD of endothelial cells is not under conventional second messenger or hormonal regulation, but that up-regulation of the enzyme is associated with (and perhaps stimulated by) free-radical or oxidant production that also may be influenced by availability of certain cytokines under replicating conditions.
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PMID:Regulation of Cu,Zn-superoxide dismutase in bovine pulmonary artery endothelial cells. 133 80

In this study we discuss the clinical value of the sequential measurement of the CSF uric acid and CSF cells in patients with postoperative acute meningitis. CSF was investigated for uric acid and cells in 10 cases with postoperative meningitis and 12 cases without it for the control group. The results were as follows; The CSF uric acid level was markedly increased in direct proportion to neutrophilia in the CSF in the acute stage of postoperative meningitis. Some cases with postoperative meningitis had biphasic increasing pattern of the CSF uric acid level. In 12 cases without postoperative meningitis the CSF uric acid level had been progressively reduced and then normalized until the fourth day after operation. The factors contributing to the increase of the uric acid in CSF under the condition of postoperative meningitis were thought to be 1) increased permeability of the blood-CSF barrier, 2) neutrophilia in the CSF and increase of the nucleic acid due to it, 3) increase of hypoxanthine, xanthine or xanthine oxidase activity in the central nervous system and 4) dysfunction of the CSF dynamics.
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PMID:[Clinical value of the sequential study of the uric acid level in the CSF in patients with postoperative meningitis]. 404 19

Our laboratory recently isolated free PQQ (2,7,9-tricarboxy-pyrroloquinoline quinone, methoxatin), a bacterial redox cofactor, from red cells, neutrophils, serum and milk and found free PQQ in CSF, synovial fluid and bile. The metabolism and functions of PQQ and ascorbate may be coupled. Physiologically, free PQQ catalyzes dioxygen-superoxide interconversion, and participates in both superoxide generation (respiratory burst) and scavenging (cell protection). Using a labeled aromatic o-diamine, superoxide formation by activated neutrophils was inhibited and the labeled phenazine adduct of PQQ could be isolated from the inhibited cells (Karnovsky et al., 1992). PQQ may convert xanthine oxidase to xanthine dehydrogenase (XD) and could be the physiological coenzyme of XD. PQQ plus copper, form a potent amine-oxidizing system. Shah et al., 1992 found that PQQ-Cu2+ catalyzes the oxidation of epsilon-amino groups in collagen and elastin. Rucker's lab (Smidt et al., 1991) has found that PQQ may be a vitamin for mouse pups. Watanabe et al., 1988 and Nishigori et al., 1989, showed that injected PQQ protects animals against oxidative stress injury. PQQ's in vivo antioxidant action, spares reduced glutathione. PQQ, as an actively transported organic anion, concentrates in cells. In other experiments (Aizenman et al., 1992), PQQ protected neurons against the neurotoxin action of the glutamate-receptor against NMDA. We shall consider possible roles for PQQ in the biosynthesis of nitric oxide (NO, endothelium-derived relaxing factor, EDRF) from L-arginine and in NO removal by superoxide. NO has now been linked to the inhibition of osteoclastic bone resorption.
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PMID:Is the antioxidant, anti-inflammatory putative new vitamin, PQQ, involved with nitric oxide in bone metabolism? 840 96

Reactive oxygen species (ROS) have been shown to stimulate proliferation and growth responses in a variety of mammalian cell types and to act as important mediators in many cellular processes, including hematolymphopoiesis. We examined the effect on primitive murine hematopoietic progenitor cells (HPC) of ROS generated by xanthine plus xanthine oxidase (xanthine/XO) and various antioxidants. Pretreatment of murine HPC (C57BL/6) with xanthine/XO produced a dose-dependent enhancement of clonogenic response to granulocyte/macrophage colony-stimulating factor (GM-CSF) but not to interleukin-3 or granulocyte colony-stimulating factor. Stem cell factor (SCF), a potent comitogen for many hematopoietic growth factors, also synergized with GM-CSF. However, the synergistic enhancement of GM-CSF with xanthine/XO and SCF was not additive, indicating that xanthine/XO and SCF may target the same subpopulation of HPC. Support for this conclusion came from experiments demonstrating that 1) mutant mice strains constitutively lacking a SCF-responsive population of HPC [White spotted (W/WV) and Steel (SI/SId)] are unresponsive to xanthine/XO- and SCF-induced enhancement of GM-CSF and 2) 3,4-epoxybutene, which selectively abrogates SCF synergy with GM-CSF, inhibits xanthine/XO-induced enhancement. As xanthine/XO can mimic SCF in this population of HPC, the possibility exists that ROS also play a role in normal SCF-mediated proliferation of these cells. To test this hypothesis, we used the antioxidants N-tert-butyl-alpha-phenylnitrone, exogenous superoxide dismutase, and catalase. Both N-tert-butyl-alpha-phenylnitrone and superoxide dismutase effectively inhibited SCF and xanthine/XO synergism with GM-CSF, whereas catalase had no effect, indicating that the superoxide anion may be involved. Also, none of these compounds affected SCF synergism with other hematopoietic growth factors, such as interleukin-3 or granulocyte colony-stimulating factor, suggesting a population-specific phenomenon. These findings indicate that xanthine/XO mimics SCF in stimulating a subpopulation of murine HPC to proliferate and that SCF synergy with GM-CSF in this population is sensitive to antioxidant inhibition.
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PMID:Reactive oxygen species mediate stem cell factor synergy with granulocyte/macrophage colony-stimulating factor in a subpopulation of primitive murine hematopoietic progenitor cells. 864 49

Amyotrophic lateral sclerosis (ALS) is a progressive neurological disease characterized by upper and lower motoneurone degeneration. Excitotoxicity and oxidative stress have been proposed as possible aetiological factors. We measured the neuronal death induced in rat cortical cell cultures by CSF taken from seven ALS patient and seven control subjects with lumbar radiculopathies. Cultures were exposed to CSF for 48 h at a dilution of 1:4. Some cultures were also exposed to antioxidant drugs, the free radical scavenger vitamin E (250 microM) and the xanthine oxidase inhibitor allopurinol (50 microM), alone or combined. The mean neuronal death rate was 31.8 +/- 3.4% in cultures exposed to ALS CSF and 10.9 +/- 1.8% in cultures exposed to control CSF. The cytotoxicity of ALS CSF was partially blocked by vitamin E (21.6 +/- 3%) or by allopurinol (18.6 +/- 2.7%). The combination of these two antioxidants reduced the toxicity from 31.8 +/- 3.4% to 10.6 +/- 1.7%. The present work suggests that neurotoxicity induced by CSF from patients with ALS indirectly involves free radicals. A combination of allopurinol and vitamin E may be useful in ALS therapy.
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PMID:Antioxidant drugs block in vitro the neurotoxicity of CSF from patients with amyotrophic lateral sclerosis. 890 5

In low concentrations, benzene and its metabolite hydroquinone are known to have diverse biological effects on cells, including the synergistic stimulation with GM-CSF of hematopoietic colony formation in vitro, stimulation of granulocytic differentiation in vitro and in vivo, and general suppression of hematopoiesis in vivo. These chemicals are also known to be active in the induction of active oxygen species. We used several assays to determine the effects of benzene metabolites (hydroquinone, benzenetriol, benzoquinone) and active oxygen species (xanthine/xanthine oxidase) on cell growth and cell cycle kinetics of the human myeloid cell line HL-60. HL-60 cells treated with these chemicals for 2 h in PBS showed increased growth over untreated controls in a subsequent 18h growth period in complete media. Incorporation of 3H-thymidine was also increased proportionately by these treatments. Catalase treatment abrogated the increased cell growth of all chemicals, suggesting an oxidative mechanism for the effect of all treatments alike. Cell cycle kinetics assays showed that the growth increase was caused by an increased recruitment of cells from G0/G1 to S-phase for both hydroquinone and active oxygen, rather than a decrease in the length of the cell cycle. Benzene metabolite's enhancement of growth of myeloid cells through an active oxygen mechanism may be involved in a number of aspects of benzene toxicity, including enhanced granulocytic growth and differentiation, stimulation of GM-CSF-induced colony formation, apoptosis inhibition, and stimulation of progenitor cell mitogenesis in the bone marrow. These effects in sum may be involved in the benzene-induced "promotion" of a clonal cell population to the fully leukemic state.
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PMID:Enhancement of myeloid cell growth by benzene metabolites via the production of active oxygen species. 1019 77

The uptake of nucleobases was investigated across the basolateral membrane of the sheep choroid plexus perfused in situ. The maximal uptake (U(max)) for hypoxanthine and adenine, was 35.51+/-1.50% and 30.71+/-0.49% and for guanine, thymine and uracil was 12.00+/-0.53%, 13.07+/-0.48% and 12.30+/-0.55%, respectively with a negligible backflux, except for that of thymine (35.11+/-5.37% of the U(max)). HPLC analysis revealed that the purine nucleobase hypoxanthine and the pyrimidine nucleobase thymine can pass intact through the choroid plexus and enter the cerebrospinal fluid CSF so the lack of backflux for hypoxanthine was not a result of metabolic trapping in the cell. Competition studies revealed that hypoxanthine, adenine and thymine shared the same transport system, while guanine and uracil were transported by a separate mechanism and that nucleosides can partially share the same transporter. HPLC analysis of sheep CSF collected in vivo revealed only two nucleobases were present adenine and hypoxanthine; with an R(CSF/Plasma) 0.19+/-0.02 and 3.43+/-0.20, respectively. Xanthine and urate, the final products of purine catabolism, could not be detected in the CSF even in trace amounts. These results suggest that the activity of xanthine oxidase in the brain of the sheep is very low so the metabolic degradation of purines is carried out only as far as hypoxanthine which then accumulates in the CSF. In conclusion, the presence of saturable transport systems for nucleobases at the basolateral membrane of the choroidal epithelium was demonstrated, which could be important for the distribution of the salvageable nucleobases, adenine and hypoxanthine in the central nervous system.
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PMID:The characteristics of nucleobase transport and metabolism by the perfused sheep choroid plexus. 1114 53

Experimental bacterial meningitis due to Streptococcus pneumoniae in infant rats was associated with a time-dependent increase in CSF and cortical urate that was approximately 30-fold elevated at 22 h after infection compared to baseline. This increase was mirrored by a 20-fold rise in cortical xanthine oxidoreductase activity. The relative proportion of the oxidant-producing xanthine oxidase to total activity did not increase, however. Blood plasma levels of urate also increased during infection, but part of this was as a consequence of dehydration, as reflected by elevated ascorbate concentrations in the plasma. Administration of the radical scavenger alpha-phenyl-tert-butyl nitrone, previously shown to be neuroprotective in the present model, did not significantly affect either xanthine dehydrogenase or xanthine oxidase activity, and increased even further cortical accumulation of urate. Treatment with the xanthine oxidoreductase inhibitor allopurinol inhibited CSF urate levels earlier than those in blood plasma, supporting the notion that urate was produced within the brain. However, this treatment did not prevent the loss of ascorbate and reduced glutathione in the cortex and CSF. Together with data from the literature, the results strongly suggest that xanthine oxidase is not a major cause of oxidative stress in bacterial meningitis and that urate formation due to induction of xanthine oxidoreductase in the brain may in fact represent a protective response.
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PMID:Marked elevation in cortical urate and xanthine oxidoreductase activity in experimental bacterial meningitis. 1133 4

Xanthine oxidase (XO), an enzyme that converts hypoxanthine to xanthine and xanthine to uric acid, is thought to contribute to hypoxic-ischemic brain injury by generating oxygen-free radicals during reperfusion. This is based largely on the observation that inhibition of XO reduces brain damage, but the precise mechanism by which the enzyme contributes to cerebral ischemic injury has not been specifically evaluated. We examined the role of XO in generating oxygen-free radicals that cause brain injury, hypothesizing that if XO generated a significant amount of free radicals during hypoxia-ischemia and reperfusion, providing additional substrate at the time of injury should increase brain damage. Anesthetized rabbits were first subjected to 8 min of cerebral hypoxia by breathing 3% oxygen and then to 8 min of ischemia by raising intracranial pressure equal to mean arterial pressure with an artificial CSF. In order to promote oxygen-free radical generation, hypoxanthine (n=9) or xanthine (n=9), XO substrates, or the vehicle (n=8) was infused intravenously beginning 30 min before and continuing until 30 min after the insult. Animals were sacrificed after 4 h of reperfusion. Neither hypoxanthine nor xanthine infusion increased brain damage. However, administration of hypoxanthine significantly improved somatosensory evoked potential recovery and preserved neurofilament 68 kDa protein, a neuronal structural protein. This study does not support free radical generation by XO as a major cause of damage in cerebral hypoxia-ischemia. Infusion of hypoxanthine reduced cerebral injury suggesting that another mechanism may explain why inhibition of XO reduces brain damage.
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PMID:The effect of infusing hypoxanthine or xanthine on hypoxic-ischemic brain injury in rabbits. 1733 86