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)

Dimalonic acid C60 (10(-5) M), a new fullerene derivative, produced an augmentation of phenylephrine-induced tone and reduced both the acetylcholine-induced maximum relaxation and the amplitude of substance P (10(-8) M)-induced relaxation in endothelium-containing thoracic aorta of rabbit; the acetylcholine- and substance P-induced relaxation was restored in the presence of superoxide dismutase (250 U/ml). Dimalonic acid C60 (10(-5) M) did not influence the phenylephrine-induced contractile response in the absence of endothelium, but the acetylcholine-induced relaxation was eliminated by removal of the endothelium. Superoxide anion generation, using hypoxanthine (1 mM)/xanthine oxidase (16 mU/ml), reduced the acetylcholine-induced relaxation and produced an augmentation of phenylephrine-induced tone in endothelium-containing strips; these effects were negated by the addition of superoxide dismutase (250 U/ml). A nitric oxide-generating agent, S-nitroso-N-acetylpenicillamine, caused relaxation of aorta without endothelium in a concentration-dependent manner, and the concentration-response curve was shifted to the right in the presence of dimalonic acid C60. This inhibitory effect of dimalonic acid C60 was also masked in the presence of superoxide dismutase. Sodium nitroprusside-induced relaxation was not affected by either dimalonic acid C60 or superoxide dismutase. These observations suggest that dimalonic acid C60 inhibits endothelium (nitric oxide)-dependent agonist-induced relaxation through the production of superoxide.
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PMID:Inhibitory effects of a fullerene derivative, dimalonic acid C60, on nitric oxide-induced relaxation of rabbit aorta. 920 May 57

Cigarette smoking is associated with peptic ulceration in humans. A mechanistic study of the potentiating effects of cigarette smoking on acetic acid-induced gastric ulceration in rats was hence performed. Rats were exposed to 0, 2 or 4% of cigarette smoke for three 1-hr periods during the 24 hr starvation before ulcer induction. Cigarette smoke exposure potentiated ulcer formation which was accompanied by a reduction of gastric blood flow at the ulcer base and ulcer margin. Further studies showed that cigarette smoke exposure alone did not cause any macroscopic injury in the stomach but significantly decreased the basal gastric blood flow in a concentration-dependent manner, which was coupled with an increase in mucosal xanthine oxidase (XO) activity. Pretreatment with allopurinol (Allo, 5 mg/kg, i.v.), a XO inhibitor, partially prevented the potentiating effect of cigarette smoke exposure on ulcer formation and also significantly improved the gastric blood flow. Ulcer induction itself dramatically increased constitutive nitric oxide synthase (cNOS) activity and prostaglandin E2 (PGE2) level in the gastric mucosa. However, the increment of cNOS activity but not PGE2 level was markedly attenuated by cigarette smoke exposure. Sodium nitroprusside (SNP, 25 or 50 microg/kg, i.v.), a nitric oxide (NO) donor, completely abolished the potentiating effect of cigarette smoke exposure on ulcer formation and also reversed the adverse effect on gastric blood flow. Thus, XO activation and cNOS reduction in the gastric mucosa are closely associated with the potentiating action of cigarette smoke exposure on ulcer formation in rats.
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PMID:Mechanistic study of adverse actions of cigarette smoke exposure on acetic acid-induced gastric ulceration in rats. 948 4

Recent studies have characterized a rebound pulmonary vasoconstriction with abrupt withdrawal of inhaled nitric oxide (NO) during therapy for pulmonary hypertension, suggesting that inhaled NO may downregulate basal NO production. However, the exact mechanism of this rebound pulmonary hypertension remains unclear. The objectives of these studies were to determine the effect of NO exposure on endothelial NO synthase (eNOS) gene expression, enzyme activity, and posttranslational modification in cultured pulmonary arterial endothelial cells. Sodium nitroprusside (SNP) treatment had no effect on eNOS mRNA or protein levels but did produce a significant decrease in enzyme activity. Furthermore, although SNP treatment induced protein kinase C (PKC)-dependent eNOS phosphorylation, blockade of PKC activity did not protect against the effects of SNP. When the xanthine oxidase inhibitor allopurinol or the superoxide scavenger 4,5-dihydroxy-1-benzene-disulfonic acid were co-incubated with SNP, the inhibitory effects on eNOS activity could be partially alleviated. Also, the levels of superoxide were found to be elevated 4.5-fold when cultured pulmonary arterial endothelial cells were exposed to the NO donor spermine/NO. This suggests that NO can stimulate xanthine oxidase to cause an increase in cellular superoxide generation. A reaction between NO and superoxide would produce peroxynitrite, which could then react with the eNOS protein, resulting in enzyme inactivation. This mechanism may explain, at least in part, how NO produces NOS inhibition in vivo and may delineate, in part, the mechanism of rebound pulmonary hypertension after withdrawal of inhaled NO.
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PMID:Nitric oxide exposure inhibits endothelial NOS activity but not gene expression: a role for superoxide. 961

Growing evidence indicates that reactive oxygen species (ROS) as well as nitric oxide (NO) have a profound influence on contractile function of skeletal muscle possibly through modulation of excitation-contraction coupling. We hypothesized that if NO and xanthine oxidase (XO) interact at key sites in excitation-contraction coupling, the effects of XO with nitric oxide synthase (NOS) inhibitors and NO donors on contractile function of the unfatigued diaphragm would not be additive. Diaphragm fibre bundles were extracted from 4-month Fischer-344 rats and placed in Krebs solution bubbled with 95% O2, 5% CO2. Baseline twitch tension, tension at 20 Hz (low-frequency), and maximal tetanic tension (Po) at 120 Hz were then measured (PRE). In Experiment 1 diaphragm fibre bundles were exposed to Krebs with 200 microM hypoxanthine as a control (CON); 0.02 U mL-1 XO + 200 microM hypoxanthine; 1 mM of the NOS inhibitor N-nitro-L-arginine (L-NNA) or L-NNA + XO. Five minutes were allowed for equilibration, and a second set of contractile measures was taken (POST). In Experiment 2 we exposed diaphragm fibre bundles to one of the following four solutions: CON, XO, 100 microM of the NO donor sodium nitroprusside (SNP) and XO + SNP, and evaluated contractile function as described above. In Experiment 3 we tested to determine if peroxynitrite production from the reaction of superoxide anion and NO affected the above results for SNP using 30 microM ebselen as a peroxynitrite quencher. Xanthine oxidase resulted in a significant potentiation of diaphragm twitch tension and tension at 20 Hz (+29%) without affecting Po. L-NNA also significantly increased 20 Hz tension but did not alter Po. However, the combination of XO + L-NNA did not further increase low-frequency contractility. Sodium nitroprusside alone did not affect diaphragm contractility, but did attenuate XO-induced potentiation in the XO + SNP group. Ebselen did not alter the impact of SNP on XO in the diaphragm. These data support the hypothesis that XO and NO interact or compete at similar sites of action that modulate contractility of the unfatigued diaphragm.
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PMID:Interaction of nitric oxide and reactive oxygen species on rat diaphragm contractility. 1088 37

We studied the effects of reactive oxygen species (ROS) on intracellular Ca2+ concentration ([Ca2+]i) and their possible modulation by nitric oxide (NO) in fura-2-loaded cultured bovine tracheal epithelium. Hypoxanthine (HX) and xanthine oxidase (XO), which generate superoxide anion (O2-) and hydrogen peroxide (H2O2), dose dependently increased [Ca2+]i. The increase in [Ca2+]i was reduced in the presence of superoxide dismutase (SOD, 200 U/mL) and catalase (200 U/mL) by 29% and 43%, respectively. The iron chelator o-phenanthroline and the hydroxyl radical (.OH) scavenger dimethylthiourea (DMTU) more potently inhibited the response of [Ca2+]i. H2O2-derived .OH generated by the Fenton reaction caused a marked [Ca2+]i elevation, but exogenous H2O2 did not. Sodium nitroprusside (100 microM), an NO donor, potentiated HX-XO-induced [Ca2+]i rise by 50%, an effect that was abolished in the presence of SOD or DMTU. These results suggest that .OH formed by interaction of O2- and H2O2 in the presence of iron may play a major role in the HX-XO-induced disruption of airway epithelial Ca2+ homeostasis, and that NO potentiates ROS-induced [Ca2+]i response, presumably by reacting with O2- and producing .OH.
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PMID:Effects of reactive oxygen species on intracellular calcium in bovine tracheal epithelium: modulation by nitric oxide. 1091 32

Hydroxylamine (HA) is a putative intermediate in the conversion of l-arginine to nitric oxide (NO). HA was reported to cause the relaxation of precontracted aorta strips; however, the ionic mechanisms of HA-induced vasorelaxation were not yet known. In the present study, the whole-cell patch-clamp technique was used to examine the effects of HA on ATP-sensitive K+ (K(ATP)) currents and membrane potentials in vascular smooth muscle cells from rat mesenteric arteries and underlying mechanisms. It was found that bath-applied HA reversibly enhanced K(ATP) currents in a concentration-dependent fashion with an EC50 of 54 +/- 3.4 microM and hyperpolarized the cell membrane from -48 +/- 5.2 to -65 +/- 7.5 mV (n = 6, p < 0.01). The increase in K(ATP) currents induced by HA was suppressed by superoxide dismutase (-380 +/- 45 to -160 +/- 20 pA, n = 4, p < 0.01) and N-acetyl-L-cysteine (-385 +/- 55 to -150 +/- 16 pA, n = 5, p < 0.01), indicating the involvement of different free radicals, including superoxide anion. Hypoxanthine/xanthine oxidase increased not only basal K(ATP) currents, but also HA-enhanced K(ATP) currents (from -355 +/- 40 to -480 +/- 62 pA, n = 6, p < 0.05). Sodium nitroprusside, a spontaneous NO donor, and a membrane-permeable cGMP analog (8-bromo-cGMP) were without effects on HA-enhanced K(ATP) currents or basal K(ATP) currents. Our results indicate that HA augmented K(ATP) channel activity and hyperpolarized cell membrane, possibly via increased free radical generation.
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PMID:The effect of hydroxylamine on KATP channels in vascular smooth muscle and underlying mechanisms. 1571 63