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)

In vitro, arachidonic acid depressed calcium transport by sarcoplasmic reticulum (SR) in the homogenate of canine masseter muscle. This effect was inhibited by superoxide dismutase (SOD), a scavenger of the superoxide anion radial ( . O-2), at pH 7.0, and by SOD plus d-mannitol, a scavenger of hydroxyl free radical ( . OH), at pH 5.5. Indomethacin and 2-aminomethyl-4-tert-butyl-6-propionyl phenol (ONO-3144), a compound known to accelerate the conversion of prostaglandin G2 (PGG2) to PGH2 and scavenge free radicals, inhibited the effect of arachidonic acid at both pH 7.0 and pH 5.5. PGG2, but not PGH2, duplicated the effect of arachidonic acid. The effect of PGG2 on SR function was similar to that of exogenous free radicals generated from the xanthine-xanthine oxidase system. Incubation at pH 5.5, in the absence of an exogenous free-radical generating system, depressed SR calcium transport in the homogenate and in isolated SR. This effect in the homogenate was inhibited by indomethacin or by ONO-3144. At 10-min incubation at pH 5.5, SOD partially and temporarily reversed the depressant effect of acidosis. The addition of SOD plus d-mannitol completely reversed the system. d-Mannitol alone was ineffective. Arachidonic acid was able to mimic these effects of acidosis, except that arachidonic acid further depressed isolated SR calcium transport. These results demonstrate that acidosis can depress SR calcium transport in the homogenate of masseter muscle by an oxygen-free radical mechanism by the generation of . O-2 and . OH. Our results also demonstrate that significant oxygen radical generation can occur through the cyclooxygenase pathway of arachidonic acid metabolism at an acidotic pH in the cellular environment outside of the SR of the muscle cell, and seems to be responsible for the generation of the . OH derived from . O-2.
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PMID:Inhibition by free radical scavengers and by cyclooxygenase inhibitors of the effect of acidosis on calcium transport by masseter muscle sarcoplasmic reticulum. 298 87

In vitro generation of free radicals by xanthine oxidase acting on hypoxanthine as a substrate induced a decreased calcium uptake velocity and reduced calcium-dependent ATPase activity of isolated sarcoplasmic reticulum (SR) vesicles from canine masseter muscle at pH 7.0. At pH 5.5 calcium uptake velocity was also reduced but ATPase activity was unaffected. Application of arachidonic acid or prostaglandin G2 induced the depression of both calcium uptake velocity and ATPase activity. The effect of arachidonic acid and prostaglandin G2 on ATPase activity depended on the pH. At pH 7.0, ATPase activity was decreased, but at pH 5.5 it was unchanged. These effects were reversed by superoxide dismutase (SOD) at pH 7.0, and by SOD plus mannitol at pH 5.5. Prostaglandin H2, prostaglandin E2 and 11,14,17-eicosatrienoic acid had no effect on calcium uptake velocity and ATPase activity at both pH 7.0 and pH 5.5. These results suggest that damage to the masseter muscle is caused by a free radical superoxide anion generated as a result of increased prostaglandins synthesis, and by the production of more lethal hydroxyl radical switched from the production of superoxide anion at low pH.
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PMID:Free radical damage to sarcoplasmic reticulum of masseter muscle by arachidonic acid and prostaglandin G2. 621 88

In bovine coronary artery segments, peroxynitrite inhibits prostacyclin (PGI2) synthase by tyrosine nitration. Using this pharmacological model, we show that a 1 h exposure of bovine coronary artery segments to endotoxin (lipopolysaccharide [LPS]) inhibits the relaxation phase following angiotensin II (Ang II) stimulation and causes a vasospasm that can be suppressed by a thromboxane A2 (TxA2) receptor blocker. In parallel, PGI2 synthesis decreases in favor of prostaglandin E2 formation. Immunoprecipitation and costaining with an anti-nitrotyrosine antibody identified PGI2 synthase as the main nitrated protein in the endothelium. All effects of LPS could be prevented in the presence of the nitric oxide (NO) synthase inhibitor Nomega-mono-methyl-L-arginine and polyethylene-glycolated Cu/Zn- superoxide dismutase. Thus, the early phase of endothelial cell activation in bovine coronary arteries by inflammatory agents proceeds by a protein synthesis-independent priming process for a source of superoxide that we tentatively attribute to xanthine oxidase. Upon receptor activation, Ang II stimulates NO and superoxide production, resulting in a peroxynitrite-mediated nitration and inhibition of PGI2 synthase. The remaining 15-hydroxy-prostaglandin 9,11-endoperoxide (PGH2) first activates the TxA2/PGH2 receptor and then is converted to prostaglandin E2 (PGE2) by smooth muscle cells. PGE2 together with a lack of NO and PGI2 is known to promote the adhesion of white blood cells and their immigration to the inflammatory locus.
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PMID:Endothelial cell activation by endotoxin involves superoxide/NO-mediated nitration of prostacyclin synthase and thromboxane receptor stimulation. 1267 Aug 82

The present study investigated the mechanisms involved in the increased 5-hydroxytryptamine (5-HT) vasoconstriction observed in rat middle cerebral arteries exposed in vitro to lipopolysaccharide (LPS, 10 microg x ml-1) for 1-5 h. Functional, immunohistochemical and Western blot analysis and superoxide anion measurements by ethidium fluorescence were performed. LPS exposure increased 5-HT (10 microm) vasoconstriction only during the first 4 h. In contrast to control tissue, indomethacin (10 microm), the COX-2 inhibitor NS 398 (10 microm), the TXA2/PGH2 receptor antagonist SQ 29548 (1 microm) and the TXA2 synthase inhibitor furegrelate (1 microm) reduced 5-HT contraction of LPS-treated arteries from hour one. The iNOS inhibitor aminoguanidine (0.1 mm) increased 5-HT contraction from hour three of LPS incubation. The superoxide anion scavenger superoxide dismutase (SOD, 100 U ml-1) and the H2O2 scavenger catalase (1000 U ml-1), as well as the respective inhibitors of NAD(P)H oxidase and xanthine oxidase, apocynin (0.3 mm) and allopurinol (0.3 mm), reduced 5-HT contraction after LPS incubation. LPS induced an increase in superoxide anion levels that was abolished by PEG-SOD. Subthreshold concentrations of the TXA2 analogue U 46619, xanthine/xanthine oxidase and H2O2 potentiated, whereas those of sodium nitroprusside inhibited, the 5-HT contraction. COX-2 expression was increased at 1 and 5 h of LPS incubation, while that of iNOS, Cu/Zn-SOD and Mn-SOD was only increased after 5 h. All the three vascular layers expressed COX-2 and Cu/Zn-SOD. iNOS expression was detected in the endothelium and adventitia after LPS. In conclusion, increased production of TXA2 from COX-2, superoxide anion and H2O2 enhanced vasoconstriction to 5-HT during the first few hours of LPS exposure; iNOS and SOD expression counteracted that increase at 5 h. These changes can contribute to the disturbance of cerebral blood flow in endotoxic shock.
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PMID:Mechanisms involved in the early increase of serotonin contraction evoked by endotoxin in rat middle cerebral arteries. 1453 51

Obesity is related to vascular dysfunction through inflammation and oxidative stress and it has been identified as a risk factor for chronic renal disease. In the present study, we assessed the specific relationships among reactive oxygen species (ROS), cyclooxygenase 2 (COX-2), and endothelial dysfunction in renal interlobar arteries from a genetic model of obesity/insulin resistance, the obese Zucker rats (OZR). Relaxations to acetylcholine (ACh) were significantly reduced in renal arteries from OZR compared to their counterpart, the lean Zucker rat (LZR), suggesting endothelial dysfunction. Blockade of COX with indomethacin and with the selective blocker of COX-2 restored the relaxations to ACh in obese rats. Selective blockade of the TXA2/PGH2 (TP) receptor enhanced ACh relaxations only in OZR, while inhibition of the prostacyclin (PGI2) receptor (IP) enhanced basal tone and inhibited ACh vasodilator responses only in LZR. Basal production of superoxide was increased in arteries of OZR and involved NADPH and xanthine oxidase activation and NOS uncoupling. Under conditions of NOS blockade, ACh induced vasoconstriction and increased ROS generation that were augmented in arteries from OZR and blunted by COX-2 inhibition and by the ROS scavenger tempol. Hydrogen peroxide (H2O2) evoked both endothelium- and vascular smooth muscle (VSM)-dependent contractions, as well as ROS generation that was reduced by COX-2 inhibition. In addition, COX-2 expression was enhanced in both VSM and endothelium of renal arteries from OZR. These results suggest that increased COX-2-dependent vasoconstriction contributes to renal endothelial dysfunction through enhanced (ROS) generation in obesity. COX-2 activity is in turn upregulated by ROS.
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PMID:COX-2 is involved in vascular oxidative stress and endothelial dysfunction of renal interlobar arteries from obese Zucker rats. 2584 78