Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:1.17.3.2 (xanthine oxidase)
8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the rabbit myocardium, ischemia (produced by ligation of the left circumflex coronary artery) is associated with a reduction in antioxidant capacity. This is reflected by an increased glutathione depletion and production of thiobarbituric acid reactive substances following in vitro oxidative challenge with t-butylhydroperoxide. This effect is greatly intensified by reperfusion following periods of ischemia longer than 20 mins, thereby paralleling the onset of irreversible injury. Chronic allopurinol pretreatment (1 mg/mL in drinking water or approximately 75 mg/kg/day for seven days prior to ligation) provides significant protection of the ischemic/reperfused myocardium to t-butylhydroperoxide induced glutathione depletion and production of thiobarbituric acid reactive substances. This protection was not associated with any significant alterations in levels of tissue ATP or in the activities of the myocardial antioxidant enzymes catalase, copper,zinc-superoxide dismutase or glutathione peroxidase, suggesting that allopurinol may exert its effects by direct radical scavenging or by some other mechanism unrelated to xanthine oxidase inhibition.
...
PMID:Altered antioxidant status in the ischemic/reperfused rabbit myocardium: effects of allopurinol. 281 60

Using paraquat, adriamycin, and anthraquinone 6-sulfonate, we have investigated the ability of radical-driven Fenton reactions to oxidize formate or deoxyribose when catalyzed by iron complexed with citrate, ADP, ATP, or pyrophosphate. Radicals were generated either radiolytically or enzymatically with xanthine oxidase or ferredoxin reductase. With each radical source, the citrate, ADP, and ATP complexes were at least 50% as active as Fe(EDTA) at catalyzing deoxyribose oxidation, and slightly less active as catalysts of CO2 formation from formate. Fe(pyrophosphate) was less efficient and in some cases inactive. Although it is not possible to definitively identify the oxidant involved, it behaved more like the hydroxyl radical than the proposed ferryl or peroxoferrous species formed in equivalent reactions catalyzed by nonchelated iron, which can oxidize deoxyribose but not formate. Chelator concentrations of 1-2 mM were required for maximum effect, which implies that the major effect of the chelators is on the reactivity of Fe2+ in the Fenton reaction with H2O2. This also suggests that any iron available physiologically could participate in the Fenton reaction in a nonchelated form, and produce a ferryl species rather than the hydroxyl radical. Reactions of the organic radicals contrast with the equivalent reactions of superoxide (Haber-Weiss reaction) for which the same iron chelates are all very inefficient catalysts. Fenton reactions driven by organic reducing radicals may therefore contribute more to the toxicity of redox cycling compounds than equivalent reactions of superoxide.
...
PMID:Radical-driven Fenton reactions: studies with paraquat, adriamycin, and anthraquinone 6-sulfonate and citrate, ATP, ADP, and pyrophosphate iron chelates. 282 82

In eucaryotic cells, immature mRNA is normally restricted to the nucleus, where it is posttranscriptionally processed to mature mRNA. The intranuclear binding site for both the immature and mature mRNA is thought to be the nuclear matrix which serves as a platform for posttranscriptional RNA maturation and transport. The selectivity of nucleocytoplasmic transport for mature mRNA species seems to be due to the selectivity of the ATP-caused release of mature mRNA from the nuclear matrix; the attachment of immature mRNA to the matrix is not altered in the presence of this nucleotide. Here we show that in the presence of superoxide radical anions (O2-), which are very likely one of the causative factors in ageing, the selection mechanism for mature mRNA at the level of nuclear matrix attachment is disturbed. In the presence of a superoxide radical-generating system (xanthine/xanthine oxidase), both the mature ovalbumin mRNA and the immature ovalbumin mRNA precursors were found to be released from the nuclear matrix of hen oviduct cells, in the absence as well as in the presence of ATP. This result was also obtained when whole, isolated nuclei preincubated with xanthine/xanthine oxidase were used. The superoxide radical-caused effect could be partially prevented by co-addition of superoxide dismutase (SOD) which dismutates O2- to H2O2 and O2. On the other hand, in the presence of antibodies against the SOD, the effect of superoxide anions on RNA-matrix attachment was enhanced and its inhibition by SOD was abolished. Our results suggest that cellular ageing may be partially caused by superoxide radical-induced release of immature mRNA from its intranuclear binding site resulting in the appearance of immature messengers in the cytoplasm. This may cause both qualitative and quantitative changes in protein synthesis. Thus, ageing may be associated not only with the expression of genes coding for proteins not characteristic for the proper state of differentiation of a given cell (as suggested by the dysdifferentiative hypothesis of ageing) but also with impaired maturation of the primary gene transcripts due to the interference of superoxide radicals, not sufficiently eliminated by antioxidant mechanisms with age, with RNA-matrix attachment.
...
PMID:Superoxide radical-induced loss of nuclear restriction of immature mRNA: a possible cause for ageing. 282 75

Our recent studies have indicated that release of ATP/ADP from platelets causes enhanced O2-. responses in stimulated neutrophils. The current investigations were designed to provide further details of this phenomenon, to determine the structure-function correlates of the adenine compounds, and to assess if the results might be explained by the formation of a single metabolic product of ATP. ATP, ADP, AMP and adenosine enhanced O2-. responses of rat neutrophils stimulated with immune complexes or formyl chemotactic peptide (FMLP) but had no effect on responses of phorbol ester-stimulated neutrophils. Similar results were obtained in human neutrophils stimulated with immune complexes; when FMLP was the agonist, the results were divergent: ATP and ADP enhanced the responses, whereas AMP and adenosine were inhibitory. In structure-function studies, hydrolytically resistant forms of ATP (and other adenine nucleotides) containing blocked or cross-linked phosphate groups were active, suggesting that hydrolysis of these compounds to a common metabolic product is not required for their effects on O2-. responses. In contrast, other chemical modifications of the ribose ring or adenine base of ATP resulted in greatly diminished activity. To further pursue the question of whether metabolism of the adenine compounds via the adenosine pathway was related to the observed effects on O2-. responses, addition to rat neutrophils of inhibitors of adenosine deaminase, S-adenosyl homocysteine hydrolase, or xanthine oxidase failed to reproduce or augment the enhancement effects of the adenine compounds on O2-. responses, suggesting that metabolism of the adenine compounds to a common product may not be a requirement for the observed effects. Although the manner by which the adenine compounds affect O2-. responses is not known, the data suggest that adenosine and adenine nucleotides have important regulatory effects on oxygen radical responses of stimulated neutrophils.
...
PMID:Regulatory effects of adenosine and adenine nucleotides on oxygen radical responses of neutrophils. 283 59

Silica particles are toxic to primary cultures of macrophages or the P388D1 cell line in vitro. Loss of viability in these model systems is accompanied by depletion of ATP content within 3 to 6 hours. The mechanisms responsible for ATP depletion will be explored in this paper. After prelabeling for 1 hour with 3H-adenine, silica-treated cells released 60-80% of their labeled acid-soluble pool into the culture medium. This release did not occur after phagocytosis of nontoxic titanium dioxide particles and was specific for purines. ATP depletion was accompanied by purine catabolism: inosine, hypoxanthine, xanthine, and uric acid were detected in the culture medium using thin layer or high-performance liquid chromatography. The final xanthine oxidase step in purine catabolism generates reactive oxygen metabolites. Silica toxicity was not prevented by the xanthine oxidase inhibitor allopurinol nor exogenous purines. It is concluded that adenine nucleotide depletion and purine catabolism are not solely responsible for irreversible injury in silica toxicity. It is hypothesized that purine catabolism and release from injured macrophages may lead to generation of reactive oxygen species, injury to surrounding tissue, and fibrosis.
...
PMID:Selective purine release from P388D1 macrophages injured by silica. 283 42

The tolerance against two different levels of enzymatically generated oxygen radicals was studied in isolated Langendorff-perfused hearts from selenium (Se)-deficient and control rats. The glutathione peroxidase activity of the Se-deficient hearts was less than 5% of that of the controls. Examination of the ultrastructure was made after random sampling using morphometric methods. Selenium-deficient hearts demonstrated some areas with myocytes with intracellular oedema. Oxygen radicals (hydrogen peroxide and superoxide) were generated by adding xanthine oxidase for 12 min (high dose: 25 U/l; low dose: 12.5 U/l) and hypoxanthine to the buffer of isolated Langendorff-perfused rat hearts. Left ventricle-developed pressure (LVDP) and high-energy phosphates (ATP and CP) were measured. After the low dose of oxygen radicals, LVDP was reduced to 32.7 +/- 6.5% (mean +/- SEM) of initial values in the Se-deficient group, but only to 58.3 +/- 8.4% in the control group (p less than 0.05). After the high dose, LVDP decreased abruptly to zero in both groups. However, ATP content was significantly (p less than 0.05) lower in Se-deficient than in control hearts. Perfusion with oxygen radicals (low dose) resulted in the appearance of mitochondrial damage in both groups, but intracellular oedema was still present only in the Se-deficient hearts. It is concluded that protection against oxygen radicals was reduced in Se-deficient hearts. This was probably due to loss of myocardial glutathione peroxidase activity.
...
PMID:The selenium-deficient rat heart with special reference to tolerance against enzymatically generated oxygen radicals. 283 46

The effect of superoxide radical on the azide-insensitive ATP-dependent Ca2+-transport by a plasma membrane (PM)-enriched fraction (F2) and an endoplasmic reticulum (ER)-enriched fraction (F3) isolated from pig coronary artery was examined using xanthine oxidase plus xanthine to generate superoxide ions. A preincubation with xanthine oxidase plus xanthine at 37 degrees C preferentially inactivated the oxalate-stimulated Ca2+ uptake by the F3 fraction rather than the phosphate-stimulated uptake by the F2 fraction, indicating that the Ca2+ pump in the ER was more susceptible to this free radical. The inactivation of the Ca2+ uptake depended on the concentrations of xanthine oxidase and xanthine in the preincubation mixture as well as on the preincubation time. Furthermore, the inclusion of superoxide dismutase in the preincubation mixture prevented the inactivation. Thus the inactivation was caused by superoxide radical. Preincubation with xanthine oxidase plus xanthine, however, altered the half-life of efflux of Ca2+ from these vesicles only marginally. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the F3 fraction showed formation of a Ca2+-dependent acid stable phosphoenzyme at 0 degree C predominantly at a protein band corresponding to 100 kDa. The level of the 100-kDa acylphosphate intermediate was inhibited in parallel with the inhibition of the Ca2+ uptake by preincubation with xanthine oxidase plus xanthine. We conclude that superoxide radical inactivates the ER Ca2+ transport by lowering the level of the phosphoenzyme.
...
PMID:Effect of superoxide radical on Ca2+ pumps of coronary artery. 284 93

With a variety of forms of ischemic and toxic tissue injury, cellular accumulation of Ca2+ and generation of oxygen free radicals may have adverse effects upon cellular and, in particular, mitochondrial membranes. Damage to mitochondria, resulting in impaired ATP synthesis and diminished activity of cellular energy-dependent processes, could contribute to cell death. In order to model, in vitro, conditions present post-ischemia or during toxin exposure, the interactions between Ca2+ and oxygen free radicals on isolated renal mitochondria were characterized. The oxygen free radicals were generated by hypoxanthine and xanthine oxidase to simulate in vitro one of the sources of oxygen free radicals in the early post-ischemic period in vivo. With site I substrates, pyruvate and malate, Ca2+ pretreatment, followed by exposure to oxygen free radicals, resulted in an inhibition of electron transport chain function and complete uncoupling of oxidative phosphorylation. These effects were partially mitigated by dibucaine, a phospholipase A2 inhibitor. With the site II substrate, succinate, the electron transport chain defect was not manifest and respiration remained partially coupled. The electron transport chain defect produced by Ca2+ and oxygen free radicals was localized to NADH CoQ reductase. Calcium and oxygen free radicals reduced mitochondrial ATPase activity by 55% and adenine nucleotide translocase activity by 65%. By contrast oxygen free radicals alone reduced ATPase activity by 32% and had no deleterious effects on translocase activity. Dibucaine partially prevented the Ca2+-dependent reduction in ATPase activity and totally prevented the Ca2+-dependent translocase damage observed in the presence of oxygen free radicals. These findings indicate that calcium potentiates oxygen free radical injury to mitochondria. The Ca2+-induced potentiation of oxygen free radical injury likely is due in part to activation of phospholipase A2. This detrimental interaction associated with Ca2+ uptake by mitochondria and exposure of the mitochondria to oxygen free radicals may explain the enhanced cellular injury observed during post-ischemic reperfusion.
...
PMID:Mechanism of calcium potentiation of oxygen free radical injury to renal mitochondria. A model for post-ischemic and toxic mitochondrial damage. 287 85

Recent studies have established a major role for oxygen-derived free radicals in post ischemic tissue injury to the intestine. During ischemia, there appears to be a calcium-triggered, protease-dependent conversion of the native xanthine dehydrogenase to a superoxide-producing xanthine oxidase. The catabolic degradation of ATP during ischemia provides an oxidizable substrate, hypoxanthine. On reperfusion, molecular oxygen is resupplied and a burst of superoxide production ensues, resulting in extensive tissue damage. The same mechanism appears to occur in myocardial ischemia. Xanthine dehydrogenase rapidly converts to the oxidase during nonperfusion in the rat heart. In the isolated perfused working rat heart model, 40 min of anoxia followed by reoxygenation results in substantial release of creatine kinase. The release of creatine kinase is blocked almost completely by pretreatment of the rats with allopurinol, a specific inhibitor of xanthine oxidase.
...
PMID:Free radicals and myocardial ischemia. The role of xanthine oxidase. 298 6

The importance of intact adenosine deaminase (ADA) activity in the generation of superoxide anion by xanthine oxidase has been disputed in studies using human neutrophils or mouse macrophages. The latter demonstrated a positive correlation between ADA activity and superoxide production during phagocytosis. The immunodeficiency in inherited ADA deficiency was related to a defect in this process. Since there is considerable interspecies variation in the tissue distribution of xanthine oxidase, the metabolism of [8-14C]deoxyadenosine (dAR), the toxic metabolite which accumulates in inherited ADA deficiency, was investigated in human peritoneal macrophages. Evaluation of the distribution of radiolabel in both cell and medium demonstrated that human macrophages with intact ADA metabolize dAR under physiological conditions to deoxyinosine and hypoxanthine exclusively. The hypoxanthine is further metabolized within the cell to ATP and GTP, via IMP. No xanthine or uric acid could be detected, confirming that in human macrophages xanthine oxidase activity is insignificant, as it is in most other human cells and tissues, except liver and intestinal mucosa. Thus production of superoxide radicals in such cells via this route would be impossible, and consequently unaffected either by ADA deficiency or the xanthine oxidase inhibitor allopurinol.
...
PMID:Superoxide radicals, immunodeficiency and xanthine oxidase activity: man is not a mouse! 298 25


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

---