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: UNIPROT:P47989 (xanthine oxidase)
8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the effect of tranilast on the growth of carrageenin-induced granulation and the increase in capillary permeability induced by inflammatory agents in rats. In the carrageenin-induced granulation model, tranilast (50 or 100-200 mg/kg, p.o.) decreased significantly and dose-dependently the weight and the hydroxyproline content of the granulation tissue. Tranilast, however, showed no effect on the healing day of locally wounded dorsal skin of rats. Triamcinolone (10 mg/kg, p.o.) also showed an inhibitory effect on the carrageenin-induced granulation model. Tranilast (50-400 mg/kg, p.o.) dose-dependently inhibited the enhancement of capillary permeability induced by the Ca ionophore A23187, bradykinin and xanthine oxidase. Moreover, tranilast (30 and 300 microM) suppressed superoxide production induced by FMLP in human neutrophils, but did not act as a superoxide scavenger. Considering that hypertrophic scar and keloid are conditions characterized by abnormal cell proliferation and excessive collagen accumulation accompanied with itch and pain, these results suggest that tranilast is useful as a therapeutic drug for hypertrophic scars and keloids.
...
PMID:[Effect of tranilast, an anti-allergic drug, on carrageenin-induced granulation and capillary permeability in rats]. 137 12

The exact mechanism whereby hypoxic pulmonary vasoconstriction (HPV) is elicited is still unsettled. We have evaluated a possible role for toxic oxygen metabolites (TOM), employing a set-up of blood-perfused isolated rat lungs. HPV reflected as pulmonary arterial pressor responses, was evoked by alternately challenging the airways with a hypoxic- and a normoxic gas mixture, resulting in gradually increasing responses until a maximum was obtained. In a sequence of responses (mean +/- s.e. mean) increasing from 2.5 +/- 0.2 kPa to 3.2 +/- 0.1 kPa, administration to the perfusate of the inhibitor of xanthine oxidase (XO), allopurinol (AP) reduced the subsequent response to 2.5 +/- 0.2 kPa (P less than 0.001). By contrast, AP did not affect vasoconstriction induced by serotonin or bradykinin. In control experiments responses continued to increase after administration of hypoxanthine (substrate of XO). Neither pretreatment with daily injections of the antioxidant vitamin E for 3 days in advance, nor addition to the perfusate of the scavenger enzymes superoxide dismutase and catalase, or dimethylsulfoxide had any impact on HPV; the subsequent responses rose at the same rate and in the same way as before. Thus, the present study has shown that AP inhibition of XO depresses HPV. This could be due either to reduced production of TOM or to accumulation of purine metabolites. The absence of inhibitory effects of quenchers of TOM refutes a role for these metabolites in the elicitation of HPV. More likely, AP inhibits HPV by interfering with the purine metabolism.
...
PMID:Allopurinol inhibits hypoxic pulmonary vasoconstriction. Role of toxic oxygen metabolites. 238 53

We previously found that the small cell fraction of isolated cells from canine gastric mucosa is a major producer of prostaglandin E2 (PGE2) and identified macrophages as the predominant cellular source. Prostaglandin-H synthase activity is dependent on the continuous presence of hydroperoxides. Because reactive oxygen metabolites may mediate mucosal injury in inflammatory or ischemic disease, we studied the release of PGE2 by isolated gastric cells during exposure to an oxygen metabolite-generating system, xanthine and xanthine oxidase. We found a concentration-dependent relationship between xanthine oxidase concentration and PGE2 production without cell lysis. The maximum PGE2 production stimulated by oxidants was equivalent to the maximum PGE2 response to bradykinin and A23187. The chief and parietal cell fractions produced very little PGE2 with xanthine oxidase concentrations that stimulated maximal PGE2 production in the small cell fraction. Uric acid did not stimulate PGE2 production. Catalase completely inhibited the response, while superoxide dismutase had a partial inhibitory effect. Hydrogen peroxide stimulated concentration-dependent PGE2 production with an ED50 of approximately 5 microM. We concluded that reactive oxygen metabolites stimulate PGE2 production by the small cell fraction of gastric mucosa.
...
PMID:Oxygen metabolites modulate prostaglandin E2 production by isolated gastric mucosal cells. 249 50

The influence of the endothelium on pulmonary venular responses to reduced oxygen tension has not been defined. To examine this question, endothelial injury was induced in small guinea pig pulmonary artery and venule segments (effective lumen radius, 174 +/- 5 and 122 +/- 2 microns, respectively) by perfusion with either a mixture of hypoxanthine (5 mM) and xanthine oxidase (0.05 U/ml) (HX/XO) or collagenase (2 mg/ml). HX/XO significantly (p less than 0.05) reduced the relaxation of precontracted pulmonary arteries by acetylcholine (ACH), bradykinin (BK), and A-23187, and the relaxations were restored by including superoxide dismutase (40 micrograms/ml) in the HX/XO solution. However, neither HX/XO nor collagenase affected vasodilation induced by ACH, BK, and A-23187 in precontracted pulmonary venules. In contrast, HX/XO significantly (p less than 0.05) augmented the sustained contraction of pulmonary venules to hypoxia (HX/XO, 3.2 +/- 1.0 mg/mm; control, 1.0 +/- 0.5 mg/mm) and anoxia (HX/XO, 35.1 +/- 6.6 mg/mm; control, 20.3 +/- 4.0 mg/mm). Collagenase also significantly (p less than 0.05) enhanced the anoxic contractions (collagenase, 36.0 +/- 3.7 mg/mm; control, 20.9 +/- 6.8 mg/mm). Superoxide dismutase (40 micrograms/ml) and catalase (323 micrograms/ml) abolished HX-XO-induced augmentation of the hypoxic and anoxic contractions of pulmonary venules. Collagenase removed 54 +/- 8% of the venular endothelium (control, 5 +/- 1%), whereas HX/XO-exposed endothelial cells contained numerous craters. Neither gossypol (5 microM) nor methylene blue (10 microM) affected pulmonary venular contractions to reduced PO2. Endothelial damage augments the PO2-dependent contractions of the pulmonary venule, and this augmentation does not appear to be due to decreased release of endothelium-derived relaxing factor.
...
PMID:Effect of endothelial injury on the responses of isolated guinea pig pulmonary venules to reduced oxygen tension. 254 70

Rat pulmonary artery endothelial cells incubated with human serum that has been complement-activated by addition of cobra venom factor reveal a pronounced conversion of xanthine dehydrogenase to xanthine oxidase. This process requires the availability of the fifth component of complement (C5) but not the presence of other components (C2 and C6-C9). The phenomenon can be reproduced by addition to endothelial cells of purified human recombinant C5a but not C5a desArg or C3a. The enzyme conversion process is relatively rapid (occurring within 5-10 min), requires the presence of intact endothelial cells, and does not require protein synthesis. Similar effects on endothelial cells have been obtained with human recombinant tumor necrosis factor alpha and the chemotactic peptide N-formyl-Met-Leu-Phe. In contrast, bradykinin, recombinant human interleukin 1 beta, and phorbol ester lack this biological activity. These findings suggest novel effects of inflammatory mediators on endothelial cells.
...
PMID:Mediator-induced activation of xanthine oxidase in endothelial cells. 280 79

The effects of oxygen metabolites (superoxide anion and hydrogen peroxide) on male Wistar rat cremasteric arterioles and the involvement of these species in the mechanism of vasodilation to arachidonic acid and bradykinin were examined by in vivo television microscopy. In the present study, xanthine oxidase-derived oxygen metabolites from endogenous substrates elicited vasodilation that was selectively and almost completely inhibited by catalase but not by superoxide dismutase. These findings implicate hydrogen peroxide as the vasoactive metabolite generated. Topical application of hydrogen peroxide itself on cremasteric arterioles caused concentration-dependent dilation over the range of 10(-7) to 10(-4) M. Responses to hydrogen peroxide concentrations of up to 10(-5) M were completely inhibited by indomethacin, suggesting that hydrogen peroxide-induced increases in vessel diameter are primarily mediated through the production of vasodilator prostaglandins. In this study, we have not found any evidence to suggest that dilator responses to arachidonic acid or bradykinin are mediated through the extracellular generation of oxygen metabolites. Hydrogen peroxide-induced vasodilation might be involved in the events linking the sensing of oxygen tension through intracellular peroxide formation to the production of vasoactive mediators in the cremasteric microcirculation.
...
PMID:Oxygen metabolites and vasodilator mechanisms in rat cremasteric arterioles. 310 59

The effect of xanthine oxidase (XO)-mediated oxidant stress on endothelial cell signal transduction was determined in bradykinin-stimulated cells loaded with the Ca+(+)-sensitive probe fura-2. Calf pulmonary artery endothelial cells were incubated with a reaction mixture containing XO (50 mU/ml) and its substrate, hypoxanthine (HX) (0.5 mM), for periods of 0.5 to 2.0 hr. HX/XO time dependently increased basal cytosolic free Ca++ ([Ca++]i) and decreased the response of [Ca++]i to bradykinin, so that incubation of cells with HX/XO for 1.5 hr or longer eliminated responsiveness to agonist. In presence of XO, HX dose dependently increased basal [Ca++]i (EC50 approximately 3 x 10(-5) M) and decreased the response of [Ca++]i to bradykinin. Sequential application of bradykinin and Ca++ to cells suspended in Ca+(+)-free/EGTA buffer was performed to characterize the effects of HX/XO on receptor-activated Ca++ entry and release of Ca++ from internal stores. HX/XO attenuated internal store Ca++ release and inhibited the bradykinin-stimulated Ca++ influx pathway in a time-dependent manner. When the HX dose was decreased by an order of magnitude, HX/XO selectively inhibited the agonist-stimulated influx pathway with little effect on internal store Ca++ release. Coincubation with superoxide dismutase tended to potentiate the effects of HX/XO, whereas catalase provided almost complete protection. Similar results to HX/XO-induced alterations in Ca++ signaling were observed when glucose-glucose oxidase (G/GO) was used as the oxidant-generating system. Inhibition of Ca++ signaling by HX/XO and G/GO occurred in the absence of decreased cell viability. Together, these results suggest that HX/XO-induced inhibition of signal transduction in endothelial cells is a function of H2O2-mediated oxidant stress and represents an early dysfunction in the process of oxidant injury.
...
PMID:Xanthine oxidase inhibits transmembrane signal transduction in vascular endothelial cells. 793 72

Reperfusion after global cardiac ischemia may injure coronary artery endothelium and lead to vasospasm and thrombosis. Oxygen-derived radicals have been implicated as mediators of this process, but the precise mechanism of injury is unknown. We hypothesized that oxygen-derived radicals impair coronary endothelial production of nitric oxide, a potent endogenous vasodilator and inhibitor of platelet adhesion. To test this theory, we developed an in vitro model of reperfusion injury in which segments of epicardial canine coronary artery were suspended in organ chambers (physiologic salt solution, 37 degrees C, 95% oxygen and 5% carbon dioxide) and exposed to oxygen-derived radicals (generated by adding xanthine [10(-4) mol/L] and xanthine oxidase [100 mU/ml] to the bathing solution for 70 minutes). After exposure to oxygen-derived radicals, epicardial coronary artery smooth muscle exhibited normal contraction to potassium ions (20 mmol/L) and prostaglandin F2 (4 x 10(-6) mol/L); also, the rings relaxed normally on exposure to isoproterenol and sodium nitroprusside (10(-9) to 10(-4) mol/L) (n = 6). In contrast, endothelium-dependent vasodilatation to receptor-dependent agonists acetylcholine and adenosine diphosphate (10(-9) to 10(-4) mol/L) was impaired as compared with the reaction of control vessels not exposed to oxygen-derived radicals (n = 18, P < 0.001, and n = 10, P < 0.002, respectively). Importantly, receptor-independent, endothelium-dependent relaxation to the calcium ionophore A23187 was normal (n = 6). Further, endothelium-dependent vasodilatation to receptor-dependent agonist bradykinin (non-nitric oxide pathway) was normal after exposure to oxygen-derived radicals. This is the first study to demonstrate that oxygen-derived radicals selectively impair receptor-dependent nitric oxide production by the coronary endothelium. Diminished nitric oxide production is a likely mechanism of vasospasm and thrombosis after reperfusion of the ischemic heart.
...
PMID:Oxygen radical-mediated vascular injury selectively inhibits receptor-dependent release of nitric oxide from canine coronary arteries. 830 70

Experiments were designed to evaluate endothelium-dependent responses of pulmonary arteries following prolonged exposure to oxygen-derived free radicals. Rings of canine pulmonary arteries with and without endothelium were suspended for measurement of isometric force in organ chambers and incubated with xanthine (10(-4)M) plus xanthine oxidase (0.015 U/ml) for 1 h in the absence and presence of either superoxide dismutase (SOD, 150 U/ml), catalase (1,200 U/ml), deferoxamine (10(-3)M), or a combination of all three scavengers. Xanthine plus xanthine oxidase caused significantly greater contractions of rings without compared with those with endothelium. In rings with endothelium, contractions were reduced by SOD or catalase but not by deferoxamine. Following 1 h of exposure to xanthine plus xanthine oxidase, endothelium-dependent relaxations to ADP were reduced but not those to bradykinin or the calcium ionophore A-23187 (calcimycin). Relaxations to ADP were not corrected by incubation with the antioxidants used singly or in combination during the exposure to xanthine plus xanthine oxidase. These results suggest that oxygen-derived free radicals generated from exogenously applied xanthine plus xanthine oxidase cause contractions of canine pulmonary arteries. In addition, even when contractions of rings with endothelium were prevented by SOD and catalase, subsequent expression of some but not all endothelium-dependent relaxations were reduced. Therefore, scavenging of oxygen-derived free radicals may prevent some but not all of the vascular injury caused by oxygen-derived free radicals.
...
PMID:Effects of prolonged exposure to oxygen-derived free radicals in canine pulmonary arteries. 876 72

Pretreatment of porcine aortic endothelial cells with high D-glucose results in enhanced endothelium-derived relaxing factor (EDRF) formation (39%) due to increased endothelial Ca2+ release (57%) and Ca2+ entry (97%) to bradykinin. This study was designed to investigate the intracellular mechanisms by which high D-glucose affects endothelial Ca2+/EDRF response. The aldose-reductase inhibitors, sorbinil and zopolrestat, failed to diminish high D-glucose-mediated alterations in Ca2+/EDRF response, suggesting that aldose-reductase does not contribute to high D-glucose-initiated changes in Ca2+/EDRF signaling. Pretreatment of cells with the nonmetabolizing D-glucose analog, 3-O-methylglucopyranose (3-OMG), mimicked the effect of high D-glucose on Ca2+ release (41%) and Ca2+ entry (114%) to bradykinin, associated with elevated EDRF formation (26%). High D-glucose and 3-OMG increased superoxide anion (O2-) formation (133 and 293%, respectively), which was insensitive to inhibitors of cyclooxygenase (5,8,11,14-eicosatetraynoic acid [ETYA], indomethacin), lipoxygenase (ETYA, gossypol, nordihydroguaiaretic acid [NDGA]), cytochrome P450 (NDGA, econazole, miconazole), and nitric oxide (NO) synthase (L-omega N-nitroarginine), while it was diminished by desferal, a metal chelator. The gamma-glutamyl-cysteine-synthase inhibitor, buthioninesulfoximine (BSO), also increased formation of O2- by 365% and mimicked the effect of high D-glucose on Ca2+/EDRF signaling. The effects of high D-glucose, 3-OMG, and BSO were abolished by co-incubation with superoxide dismutase. Like high D-glucose, pretreatment with the O2(-)-generating system, xanthine oxidase/hypoxanthine, elevated bradykinin-stimulated Ca2+ release (+10%), Ca2+ entry (+75%), and EDRF (+73%). We suggest that prolonged exposure to pathologically high D-glucose concentration results in enhanced formation of O2-, possibly due to metal-mediated oxidation of D-glucose within the cells. This overshoot of O2- enhances agonist-stimulated Ca2+/EDRF signaling via a yet unknown mechanism.
...
PMID:High D-glucose-induced changes in endothelial Ca2+/EDRF signaling are due to generation of superoxide anions. 882 76


1 2 3 4 Next >>

---