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)

Oxygen free radicals have been implicated as mediators of cellular injury in ischemia-reperfusion. Since intracellular Ca(2+)-overload has been considered to play a crucial role in ischemia-reperfusion injury, this study was undertaken to examine the effects of oxygen free radicals on Ca(2+)-stimulated Mg(2+)-dependent ATPase activities and ATP-dependent Ca2+ accumulation in rat cardiac sarcolemmal membranes in vitro. Isolated rat heart sarcolemmal membranes were incubated with xanthine (X) + xanthine oxidase (XO) and assayed for Ca(2+)-pump activities. X + XO inhibited the Ca(2+)-pump activities in a time-dependent manner; a significant inhibition of Ca(2+)-stimulated ATPase activity was seen after one min of incubation. Superoxide dismutase showed a protective effect on depression in Ca(2+)-pump activities due to X + XO. To understand the involvement of sulfhydryl groups changes in causing depression of Ca(2+)-pump activities, the effects of oxygen free radicals on heart sarcolemmal sulfhydryl groups were also investigated. Heart sarcolemmal sulfhydryl groups were decreased by X + XO in a time-dependent manner. Superoxide dismutase showed a protective effect on sulfhydryl group depression caused by X + XO. N-ethylmaleimide, a sulfhydryl reagent, showed inhibitory effect on Ca(2+)-pump activities both in a time-, and a dose-dependent manner; dithiothreitol and cysteine prevented changes in Ca(2+)-pump activities caused by N-ethylmaleimide. The inhibitory effect of X + XO on Ca(2+)-pump activities were also prevented by the addition of dithiothreitol or cysteine. A significant correlation between changes in sarcolemmal Ca(2+)-stimulated ATPase activity and sarcolemmal sulfhydryl groups was seen.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Inhibition of heart sarcolemmal Ca(2+)-pump activity by oxygen free radicals. 202 66

Reactive O2 species appear to be generated both during hypoxia and at reoxygenation, but it has not been established whether these species interact with heart tissue and cause injury. Oxidative changes were evaluated in isolated rat heart perfused with Krebs-Henseleit medium containing 10 mM glucose and 2.5 mM calcium. After 5-10 min hypoxia, tissue glutathione (GSH) decreased while glutathione disulfide (GSSG), protein carbonyls, and thiobarbituric acid reactive substances (TBARS) increased compared with controls. Similarly, sarcolemmal and sarcoplasmic reticular Ca-ATPase activity (an enzyme susceptible to oxidative inactivation) decreased in response to 10 min hypoxia. These changes were more pronounced after 60 min of hypoxia when protein-GSH mixed disulfides were also increased. There were no further oxidative changes after 4 min reoxygenation when the release of lactate dehydrogenase (LDH) was maximal. Myocardial protein thiol and alpha-tocopherol contents were not significantly changed by either hypoxia or reoxygenation. Mitochondria also exhibited oxidative changes but with more pronounced increases in GSSG and mixed disulfides. There was no change in GSH or GSSG efflux into the coronary effluent during hypoxia, although, in parallel with LDH release, both increased after reoxygenation. Diamide (200 microM), t-butylhydroperoxide (20 microM), or purine (2.3 mM) + xanthine oxidase (0.01 U/ml) were infused for 10 min. Except for large diamide-induced changes in protein thiols and mixed disulfides, the magnitude of the changes produced by these oxidants was similar to those produced by hypoxia. These data show that changes consistent with oxidative processes occur in whole heart and mitochondria in response to hypoxia. The absence of marked signs of oxidation at reoxygenation suggest that enzyme release at this time is unrelated to oxidative stress.
...
PMID:Oxidative changes in hypoxic rat heart tissue. 203 61

Tissue changes consistent with oxidative damage in hypoxic/reoxygenated heart tissue have not been well documented. We recently reported that oxidative perturbations were evident in isolated-perfused rat heart tissue subjected to as little as 10 min hypoxia and that these changes were not exacerbated by reoxygenation. The mechanism and species specificity of this finding is not known. Rabbit hearts, which lack measurable xanthine oxidase activity, were examined for evidence of hypoxia-induced injury. The release of lactate dehydrogenase into the coronary effluent gradually increased during the retrograde perfusion of isolated rabbit hearts with hypoxic medium (containing 10 mM glucose and 2.5 mM calcium), and was slightly enhanced upon reoxygenation after 60 min hypoxia. Cardiac glutathione content decreased significantly while glutathione disulfide, protein-glutathione mixed disulfides, thiobaribturic acid reactive substances (TBARS), and protein carbonyl contents increased significantly after 60 min of hypoxia, compared to oxygenated controls. These values were unaltered after 4 min of reoxygenation except for a loss of TBARS. The oxidative changes observed in hypoxic rabbit hearts may be caused by energy deficiency impairing normal reductive processes or by the generation of reactive oxygen species as a result of abnormal cell functions, but cannot be related to xanthine oxidase activity.
...
PMID:Oxidative changes in hypoxic-reoxygenated rabbit heart: a consequence of hypoxia rather than reoxygenation. 206 Aug 63

The effect of organ flushing with the calcium entry blocker verapamil on the conversion of innocent enzyme xanthine dehydrogenase (XDH) to superoxide generating enzyme xanthine oxidase (XOD) in ischemic rat livers was studied. This enzyme conversion progressed over time in warm or cold ischemia. In non-flushed livers, the activities of XOD as percentages of XDH plus XOD after 6 h at 37 degrees C and 6 days at 4 degrees C were 80.3 +/- 5.2 and 31.6 +/- 2.1, respectively. In the livers flushed with Euro-Collins solution, the conversion was inhibited to 37.0 +/- 3.9% (P less than 0.001) after 6 h of warm ischemia, while this inhibitory effect was not found in cold ischemia. Verapamil given through the portal vein on flushing further suppressed the conversion in both warm and cold ischemia (with 5.0 microM of verapamil, 21.2 +/- 5.8% (P less than 0.001) after 6 h of warm ischemia and 25.2 +/- 3.3% (P less than 0.01) after 6 days of cold ischemia). A similar effect was also obtained with the addition of 10 or 30 mM of EGTA instead of verapamil. In contrast, no inhibitory effect on conversion was obtained in livers flushed and homogenized with 10.0 microM of verapamil followed by incubation for 6 h at 37 degrees C. In the livers that were flushed and stored at a warm temperature for 6 h, verapamil reduced the increase of tissue lipid peroxidation product (P less than 0.02) after 15 min of reperfusion. Although the precise mechanisms of these inhibitory effects of verapamil on the enzyme conversion are still uncertain, it is thought that organ flushing with verapamil might reduce the XOD-mediated postischemic reperfusion injury in livers subjected to prolonged ischemia.
...
PMID:Effect of verapamil on conversion of xanthine dehydrogenase to oxidase in ischemic rat liver. 208 35

Indapamide, a nonthiazide diuretic, exhibits direct vasodilator action as well as natriuretic and diuretic effects. Although calcium antagonist-like activity has been addressed so far, the mechanisms for vasodilator effect are still uncertain. To understand the wide range of indapamide actions, we examined the effects of indapamide on the vascular eicosanoid generation and investigated its mechanisms by using rat vascular smooth muscle cells in culture. Indapamide uniquely increased the prostacyclin generation in the vascular smooth muscle cells in a dose-dependent manner, whereas it did not affect the vasoconstrictor thromboxane A2. Thiazide diuretics lowered the prostacyclin generation, while nonthiazide derivatives did not affect the biosynthesis. Enzymatic analysis revealed that indapamide affected neither [14C]arachidonate liberation nor prostacyclin synthase of the smooth muscle cells. Indapamide eliminated a stable free radical in a cell-free system, lowered the formation of malondialdehyde from lipid peroxides in rat brain homogenate, and reduced lipid peroxidation by the free radical generating system of xanthine-xanthine oxidase. Indeed, the scavenging action of indapamide significantly attenuated the inhibitory activity of 15-hydroperoxy-arachidonate to prostacyclin synthase activity. These results indicate that indapamide diuretic increases prostacyclin generation in the vascular smooth muscle cells possibly through antioxidant effects and that the enhanced prostacyclin generation is partly responsible for its direct vasodilator action.
...
PMID:Radical scavengers of indapamide in prostacyclin synthesis in rat smooth muscle cell. 210 10

Using a left lung orthotopic isograft model in AS strain rats, we have investigated ultrastructural changes in lungs preserved for 48 h at 0 degrees C after a simple flush technique. Lungs were examined after storage alone and after storage followed by up to 1 h reperfusion with blood in vivo. Grafts were flushed with either isotonic saline (NaCl) or hypertonic citrate solution (HCA) alone, or with HCA containing either verapamil (a Ca2+ channel blocker), desferrioxamine (a Fe2+ antagonist), prostacyclin PGI2, nifedipine (a Ca2+ channel blocker) or allopurinol (a xanthine oxidase inhibitor). These agents were also given intravenously to both donor and recipient. Storage in NaCl produced gross cytoplasmic swelling and disruption with widespread nuclear injury. Reperfusion for 1 h resolved cell swelling but some endothelial loss and alveolar capillary wall rupture were seen. HCA with or without additional agents protected against cell swelling but endothelial blebbing and widening of the basement membrane occurred. Reperfusion for 1 h led to recovery of the basement membrane thickness but widespread endothelial loss was observed which was reduced by the addition of verapamil, desferrioxamine, nifedipine or allopurinol to the flush, but not by prostacyclin. Examination of lungs reperfused for shorter periods (5 and 15 min) identified three main types of damage to the vascular endothelium: (1) gross cell swelling, (2) detachment of intact endothelial cells from the underlying basal lamina, and (3) attenuation of cytoplasm due to blebbing. The results suggest that endothelial injury occurring on reperfusion is partly Fe2+ and Ca2(+)-mediated and that reactions catalysed by xanthine oxidase (which include oxygen free radical production) may also be important.
...
PMID:Ultrastructural changes in rat lungs after 48 h cold storage with and without reperfusion. 211 17

Oxygen-derived free radicals have been implicated in damage to membrane phospholipids leading to alterations in membrane function. The purpose of this study was to investigate alterations in intracellular ionic calcium (Ca2+) levels and Ca2+ transients, cellular morphology, conjugated diene levels, arachidonate release, and lactate dehydrogenase release resulting from the exposure of cultured neonatal rat ventricular myocytes to a xanthine oxidase catalyzed free radical generating system capable of producing superoxide and hydroxyl radicals. The ability of alpha-tocopherol to prevent alterations due to free radical exposure was investigated. For measurements of Ca2+, myocytes grown on coverslips for 3-4 days were loaded with fura-2/AM and studied by microspectrofluorometry. Control myocytes superfused with a physiological buffer or buffer containing purine and iron-loaded transferrin exhibited Ca2+ transients associated with spontaneous contractions. For control, buffer perfused myocytes (n = 4), the fura-2 340/380 ratios were 0.5 +/- 0.1 (mean +/- S.E.) and 1.6 +/- 0.03 at the minimum and maximum, respectively, of the Ca2+ transient, after 1 h of perfusion. Exposure to the free radical generating solution (n = 14) altered intracellular Ca2+. The 340/380 minimum ratio was 639% of the control value after approximately 30-70 mins with cessation of normal Ca2+ transients. Bleb development was associated with increased Ca2+. Myocytes reperfused with control medium continued to exhibit an elevated minimum fura-2 ratio at 687% of control. Myocytes pretreated with 10 microM alpha-tocopherol (n = 13) for 18-24 h and exposed to free radicals did not exhibit increases in intracellular Ca2+, having a minimum 340/380 ratio of 0.5 +/- 0.1 after 60-90 mins, and although myocytes often ceased contracting, they resumed spontaneous Ca2+ transients with control medium reperfusion and also maintained normal structure. Exposure of myocyte cultures to free radical generating solutions resulted in increased levels of conjugated dienes and increased release of [3H]arachidonate and lactate dehydrogenase compared to control values after 1 h. alpha-Tocopherol treatment attenuated the increase in conjugated diene levels, and the release of [3H]arachidonate and lactate dehydrogenase. Thus, free radicals alter intracellular Ca2+, conjugated dienes and membrane structure indicating their ability to induce altered ionic homeostasis in association with myocardial membrane damage. alpha-Tocopherol decreased free radical mediated injury.
...
PMID:Free radicals alter ionic calcium levels and membrane phospholipids in cultured rat ventricular myocytes. 212 94

A novel modulatory site on the N-methyl-D-aspartate (NMDA) receptor that is sensitive to sulfhydryl redox reagents was recently described. Here we report that this redox modulatory site is susceptible to oxidation by reactive oxygen species endogenous to the CNS. Oxygen free radicals generated by xanthine and xanthine oxidase were observed to decrease NMDA-induced changes in intracellular free Ca2+ concentrations and NMDA-evoked cation currents in cortical neurons in culture. Additionally, a sublethal production of free radicals by xanthine and xanthine oxidase reversed a dithiothreitol-induced enhancement of NMDA-mediated neurotoxicity in vitro. These results show that NMDA receptor function is modulated at its redox site by endogenous substances that normally accompany tissue reperfusion following an ischemic event. This novel mechanism for NMDA receptor regulation may have profound implications in the outcome of glutamate neurotoxicity in vivo.
...
PMID:Oxygen free radicals regulate NMDA receptor function via a redox modulatory site. 214 89

Effects of oxygen free radicals on Ca2+/Mg2+ ATPase and ATP-independent Ca2(+)-binding activities were examined in rat heart sarcolemma. Membranes were incubated with different oxygen radical generating media such as xanthine + xanthine oxidase, hydrogen peroxide, and hydrogen peroxide + Fe2+. In the presence of xanthine + xanthine oxidase, Ca2+ ATPase activity was stimulated and this effect was prevented by the addition of superoxide dismutase. Hydrogen peroxide also showed a significant increase in Ca2(+)-ATPase activity in a dose-dependent manner and this effect was blocked by catalase. On the other hand, a combination of hydrogen peroxide + Fe2+ decreased Ca2(+)-ATPase activity; this depression was prevented by the addition of D-mannitol. The observed change in Ca2(+)-ATPase activity due to oxygen free radicals was associated with changes in Vmax, whereas Ka remained unaffected. Both xanthine + xanthine oxidase and hydrogen peroxide increased whereas, hydrogen peroxide + Fe2+ inhibited the ATP-independent Ca2(+)-binding activities. It is suggested that oxygen free radicals may influence Ca2+ movements in the cell by altering the Ca2+/Mg2+ ATPase and Ca2(+)-binding activities of the membrane and these effects may be oxygen-radical species specific.
...
PMID:Alterations in heart sarcolemmal Ca2(+)-ATPase and Ca2(+)-binding activities due to oxygen free radicals. 215 97

Two possible reasons for the structural alterations of cell membranes caused by free radicals are lipid peroxidation and an increase in the intracellular calcium ion concentration. To characterize the alterations in membrane molecular dynamics caused by oxygen-derived free radicals and calcium, human erythrocytes were spin-labeled with 5-doxyl stearic acid, and alterations in membrane fluidity were quantified by electron spin resonance spectrometry. The in vitro generation of oxygen free radicals, using hypoxanthine (0.43 mM) plus xanthine oxidase (0.07 U/mL) decreased membrane fluidity, and the addition of superoxide dismutase and catalase inhibited the effect on membrane fluidity of the hypoxanthine-xanthine oxidase system. Hydrogen peroxide (0.1 and 1 mM) also decreased membrane fluidity and caused alterations to erythrocyte morphology. In addition, a decrease in membrane fluidity was observed in erythrocytes incubated with 2.8 mM CaCl2. On the other hand, incubation of erythrocytes with calcium-free solution decreased the changes in membrane fluidity caused by hydrogen peroxide. These results suggest that changes in membrane fluidity are directly due to lipid peroxidation and are indirectly the result of increased intracellular calcium concentration. We support the hypothesis that alterations of the biophysical properties of membranes caused by free radicals play an important role in cell injury, and that the accumulation of calcium amplifies the damage to membranes weakened by free radicals.
...
PMID:Alterations of human erythrocyte membrane fluidity by oxygen-derived free radicals and calcium. 216 49


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

---