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)

Reperfusion injury occurs during open-heart surgery after prolonged cardioplegic arrest. Cardiopulmonary bypass also is known to cause hemolysis. Since reperfusion of ischemic myocardium is associated with the generation of oxygen free radicals, and since free radicals can attack a protein molecule, it seems reasonable to assume that hemolysis might be the consequence of free radical attack on hemoglobin protein. The results of this study demonstrated that reperfusion following ischemic arrest caused an increase in free hemoglobin and free heme concentrations, simultaneously releasing free iron and generating hydroxyl radicals. In vitro studies using pure hemoglobin indicated that superoxide anion generated by the action of xanthine oxidase on xanthine could release iron from the heme ring and cause deoxygenation of oxyhemoglobin into ferrihemoglobin. This study further demonstrated that before the release of iron from the heme nucleus, oxyhemoglobin underwent deoxygenation to ferrihemoglobin. The released iron can catalyze the Fenton reaction, leading to the formation of cytotoxic hydroxyl radical (OH.). In fact, the formation of OH. in conjunction with hemolysis occurs during cardiac surgery, and when viewed in the light of the in vitro results, it seems likely that oxygen-derived free radicals may cause hemolysis during cardiopulmonary bypass and simultaneously release iron from the heme ring, which can catalyze the formation of OH..
Mol Cell Biochem 1992 Apr
PMID:Oxygen-derived free radicals and hemolysis during open heart surgery. 158 46

The protein-bound polysaccharide of Coriolus versicolor QUEL (PS-K) has been found to express antioxidant activity as an "ion-radical scavenger" in diamine oxidation reactions. The mode of this expression was examined to determine whether the drug functioned as a simple radical scavenger or mimicked the action of superoxide dismutase (SOD). The latter was confirmed in both enzymatic and nonenzymatic superoxide anion radical (O2-.) producing systems in vitro. The SOD mimetic activity of PS-K was demonstrated by quantitative analysis of hydrogen peroxide as the end product of O2-., its formation being assisted catalytically by SOD or PS-K. Analysis by electron spin resonance also confirmed the SOD mimetic activity of PS-K in a xanthine-xanthine oxidase reaction. Relative SOD activity with PS-K was approximately 1/8,000 in a KO2-O2-.-producing system. The SOD mimetic activity of PS-K resisted treatment by 0.7N HCl, 0.7N NaOH, boiling for 30 minutes in a double water bath, and digestion by pronase. Fractionation according to differences in molecular mass caused no significant increase in relative SOD activity within a certain range of molecular mass, indicating that there is no definite molecule expressing SOD mimetic activity. Tumor-bearing rats and human patients with digestive tract cancer who suffered from oxidative stress were relieved by a single intraperitoneal administration of PS-K or a 1-day peroral prescription.
Mol Biother 1992 Mar
PMID:Mimicking of superoxide dismutase activity by protein-bound polysaccharide of Coriolus versicolor QUEL, and oxidative stress relief for cancer patients. 162 73

The rates of NADH oxidation in presence of xanthine oxidase increase to a small and variable extent on addition of high concentrations of lactate dehydrogenase and other dehydrogenases. This heat stable activity is similar to polyvanadate-stimulation with respect to pH profile and SOD sensitivity. Isocitric dehydrogenase (NADP-specific) showed heat labile, SOD-sensitive polyvanadate-stimulated NADH oxidation activity. Polyvanadate-stimulated SOD-sensitive NADH oxidation was also found to occur with riboflavin, FMN and FAD in presence of a non-specific protein, BSA, suggesting that some flavoproteins may possess this activity.
Mol Cell Biochem 1991 Sep 18
PMID:Stimulation of NADH oxidation by xanthine oxidase and polyvanadate in presence of some dehydrogenases and flavin compounds. 178 72

Experiments were performed to investigate the hypothesis that exposure of vascular endothelial cells to low levels of reduced oxygen products results in DNA strand breakage as an early event and to determine if endothelial cells derived from bovine pulmonary artery demonstrate a susceptibility to oxidant injury that is different from that of cells derived from bovine aorta. Endothelial cells grown in culture were exposed to H2O2 (either added directly or generated from glucose oxidase) or superoxide radical (generated from xanthine oxidase), and DNA strand breakage was determined using fluorescent analysis of DNA unwinding. Cell injury was also assessed by measuring the release of lactate dehydrogenase (LDH) or the release of 51Cr from prelabeled cells. Whereas LDH or 51Cr release detected injury resulting from exposure of endothelial cells to greater than or equal to 100 microM H2O2 and was apparent only 2 or more h after exposure, DNA strand breakage was detectable after 15 min of exposure of endothelial cells to 50 microM H2O2. Approximately equivalent DNA strand breakage resulted from exposure to 50 microM H2O2, to 25 mU glucose oxidase, or to 10 mU xanthine oxidase; this injury is similar to that seen following exposure to 10 gray X-radiation. DNA strand breakage following exposure of cells to xanthine oxidase was preventable by catalase but not by superoxide dismutase or hydroxyl radical scavengers, suggesting that H2O2 is the active extracellular oxidant mediating DNA strand breaks. No differences were seen in the susceptibility of pulmonary artery or aortic endothelial cells to oxidant injury.
Am J Respir Cell Mol Biol 1991 Jan
PMID:DNA strand break formation following exposure of bovine pulmonary artery and aortic endothelial cells to reactive oxygen products. 189 51

An increased formation of oxygen free radicals in the reperfused rat small intestine is concluded from accumulations of oxidized glutathione, of thiobarbituric acid-reactive substances and of 4-hydroxynonenal. Xanthine oxidase inhibition prevented these biochemical changes. The histological and electronmicroscopic studies of intestinal sucosa showed significant structural deteriorations already at the end of the ischemic period obviously due to disturbances of cellular energy metabolism. The extent of dosage was increased during the reperfusion without qualitative changes of the pattern of structural dosage. The beneficial effects of oxypurinol on biochemical criteria which occurred already in the early phase of reperfusion were not reflected in significant morphological differences within the first hour of reperfusion. Differences of morphological findings between oxypurinol-treated and untreated animals could be observed after longer periods of reperfusion--during the regeneration of the tissue.
Cell Mol Biol 1991
PMID:Discrepancy between biochemical normalization and morphological recovery of jejunal mucosa during postischemic reperfusion in presence of the xanthine oxidase inhibitor oxypurinol. 187 27

Airway inflammation is often accompanied by accumulation of polymorphonuclear leukocytes (PMN) as well as epithelial sloughing. To determine whether PMN contribute to epithelial damage in inflammatory states, we examined the interaction of PMN and tracheal epithelial cells in culture. Ferret tracheal epithelial (FTE) cells were grown in primary culture on collagen-coated multiwell dishes. Confluent monolayers were loaded with [51Cr]O4 and exposed to resting and activated neutrophils. There was no significant increase in cell death as assessed by [51Cr]O4 release over 8 h of exposure, at effector (PMN)-to-target cell (epithelial cell) ratios up to 90:1, whether PMN were activated by maximal activating concentrations of phorbol myristate acetate or formylmethionylleucylphenylalanine with or without cytochalasin B. This result was confirmed by using a [3H]leucine release assay as well as by uptake of a supravital dye. However, exposure of FTE cells to activated PMN for 4 h resulted in separation of adjacent cells and formation of gaps in the monolayer, without significant detachment of epithelial cells from the dish. Gap formation was prevented by alpha 1-antitrypsin, N-methoxysuccinyl-Ala-Ala-Pro-Val-chloromethylketone, or 10% serum, was mimicked by PMN elastase (24 micrograms/ml), but not by hydrogen peroxide in concentrations up to 10 mM, or superoxide generated by xanthine/xanthine oxidase, and was reversible within 24 h of removal of elastase and exposure to fresh medium. We conclude that activated PMN do not kill FTE cells in culture. However, disruption of the epithelial cell monolayer probably by a proteolytic mechanism can result from exposure to activated PMN and may allow alteration of the epithelial barrier during airway inflammation.
Am J Respir Cell Mol Biol 1991 Aug
PMID:Ferret tracheal epithelial cells grown in vitro are resistant to lethal injury by activated neutrophils. 189 42

The potential role of oxidative stress conditions in the induction of heat shock proteins was studied in human umbilical vein endothelial cells. We compared the effects of temperature (43 to 45 degrees C), exposure to hydrogen peroxide (H2O2) and oxygen metabolites generated by the enzyme system hypoxanthine-xanthine oxidase (O2- plus H2O2), as well as exposure to 95% O2, on the expression of the major 70-kD heat shock proteins (hsp70). Northern blot analysis indicated that: (1) heat shock induced a rapid and marked increase in hsp70 mRNA levels that reached a maximum during recovery from a 30-min exposure to 45 degrees C; (2) treatment with a 5-mM H2O2 bolus or 50 mU/ml xanthine oxidase also increased hsp70 mRNA levels but to a lesser extent than heat shock (about 10 and 25 times less, respectively); (3) no change was detected after a 5-day exposure to 95% O2. Nuclear run on transcription data and kinetics of mRNA decay in the presence of actinomycin D indicated that the observed increase in hsp70 mRNA levels in both heat-shocked and H2O2-treated cells was mainly due to a transcriptional induction. The kinetics of hsp70 synthesis correlated with the accumulation of hsp70 mRNA. Two-dimensional gel electrophoresis and immunologic analysis of these heat shock proteins revealed a series of at least five distinct hsp70 isoforms induced in heat-shocked cells, whereas only a specific subset of these proteins, mainly one acidic isoform, was induced in very low amounts in response to H2O2 treatment. These results clearly indicate that the endothelial cell responses to oxidative stress and heat shock differ in both qualitative and quantitative terms in respect to hsp70 induction. They also suggest that the intensity of this response to oxidative stress conditions may vary depending on the nature of the oxidative challenge.
Am J Respir Cell Mol Biol 1991 Sep
PMID:Differential expression of hsp70 stress proteins in human endothelial cells exposed to heat shock and hydrogen peroxide. 191 Aug 12

Although cardiac dysfunction due to ischemia-reperfusion injury is considered to involve oxygen free radicals, the exact manner by which this oxidative stress affects the myocardium is not clear. As the occurrence of intracellular Ca2+ overload has been shown to play a critical role in the genesis of cellular damage due to ischemia-reperfusion, this study was undertaken to examine whether oxygen free radicals are involved in altering the sarcolemmal Ca2(+)-transport activities due to reperfusion injury. When isolated rat hearts were made globally ischemic for 30 min and then reperfused for 5 min, the Ca2(+)-pump and Na(+)-Ca2+ exchange activities were depressed in the purified sarcolemmal fraction; these alterations were prevented when a free radical scavenger enzymes (superoxide dismutase plus catalase) were added to the reperfusion medium. Both the Ca2(+)-pump and Na(+)-Ca2+ exchange activities in control heart sarcolemmal preparations were depressed by activated oxygen-generating systems containing xanthine plus xanthine oxidase and H2O2; these changes were prevented by the inclusion of superoxide dismutase and catalase in the incubation medium. These results support the view that oxidative stress during ischemia-reperfusion may contribute towards the occurrence of intracellular Ca2+ overload and subsequent cell damage by depressing the sarcolemmal mechanisms governing the efflux of Ca2+ from the cardiac cell.
Mol Cell Biochem 1990 Dec 20
PMID:Alterations in cardiac membrane Ca2+ transport during oxidative stress. 196 45

In the reoxygenated hypoxic heart, hypoxanthine is either oxidized by xanthine oxidase with production of toxic oxygen species or salvaged for the ATP pool by hypoxanthine-guanine phosphoribosyl transferase. To characterize the repartition of hypoxanthine between the two pathways, we have subjected rat hearts to 20 min hypoxia and monitored the recovery (ventricular, end-diastolic and coronary pressures, and the contraction rate) during the reoxygenation (30 min) in the presence of either hypoxanthine or guanine alone, or both. The rate-pressure product recovered 78% of the pre-hypoxia values in hearts reoxygenated with 100 microM hypoxanthine and 80% in hearts reoxygenated with 100 microM guanine, in contrast to 49% in the presence of both hypoxanthine and guanine (100 microM each). Thus, it is likely that hypoxanthine is salvaged when present alone and is oxidized generating the reperfusion injury when the salvage is prevented by guanine that competes with hypoxanthine from the same site of hypoxanthine-guanine phosphoribosyl transferase. The functional impairment was slower when hypoxanthine was replaced by xanthine, and was eliminated by superoxide dismutase and catalase, indicating that the injury is caused by toxic oxygen species generated from hypoxanthine and xanthine oxidase. These data suggest that the salvage pathway may be critical in preventing the reperfusion injury in hypoxic hearts.
J Mol Cell Cardiol 1991 Jan
PMID:Dual role of hypoxanthine in the reoxygenation of hypoxic isolated rat hearts. 203 69

The pathogenesis of post-ischaemic depression of contractility in myocardium was examined in isovolumic rat heart. 31P-NMR was used to monitor changes in ATP, creatine phosphate (CrP), inorganic phosphate (Pi), and [H+] during brief periods of ischaemia and reperfusion with and without allopurinol treatment. During 5, 10, or 15 min of total global ischaemia, the decline in function (rate-pressure product) correlated inversely with [Pi] (r = 0.92, P less than 0.01). Cardiac function exhibited a slow progressive recovery during 20 min of reperfusion, ultimately reaching only 85%, 78%, and 69% of its pre-ischaemic value following 5, 10, and 15 min of global ischaemia respectively. Following each ischaemic period [ATP], [CrP], [Pi], and [H+] all recovered to control levels within 5-10 min of initiating reperfusion. Allopurinol (2 mM) treatment of hearts made ischaemic for 15 min significantly improved contractile recovery to 89 +/- 7%. Allopurinol also exhibited significant anti-arrhythmic activity during the reperfusion period, decreasing the incidence of premature contractions and the duration of tachy-arrhythmias. Allopurinol had no effect on the final repletion of [ATP] and [CrP], or the recovery of [Pi] and [H+], although the rate of ATP repletion was elevated in the initial 5 min of reperfusion. These results show that neither depletion of the cytosolic high-energy phosphate pool, nor sustained elevations in [Pi] or [H+] are important in the production of post-ischaemic contractile impairment. The beneficial action of allopurinol suggests that xanthine oxidase derived oxygen free-radicals may be involved in the sustained contractile dysfunction following brief ischaemic episodes.
J Mol Cell Cardiol 1990 Oct
PMID:Behaviour of energy metabolites and effect of allopurinol in the "stunned" isovolumic rat heart. 209 34


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