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)

The effect of oxidant stress on the active transport of serotonin (5-HT) into mouse platelets was examined. Oxidant stress was produced using either H2O2 or the xanthine-xanthine oxidase generating system that yields both superoxide anion and H2O2. H2O2 (6.25-100 microM) caused a rapid (2-4 min) stimulation of platelet 5-HT transport that returned to control levels after 15 min of incubation. Catalase (1500 U/ml) completely prevented the stimulation, and the hydroxyl radical trapping agents mannitol (1 nM) and thiourea (1 mM) failed to alter the stimulation. Fluoxetine (1 microM) totally blocked all 5-HT uptake into stimulated platelets. The xanthine-xanthine oxidase (3.12-25 mU/ml) generating system produced a response similar to that of H2O2. In this system, superoxide dismutase (250 U/ml) did not alter the stimulatory response, whereas catalase (1500 U/ml) totally prevented the stimulation. The kinetics of 5-HT transport showed that oxidant stress did not alter the Km of 5-HT transport (Km control = 8.0 +/- 1.0 x 10(-7) M versus Km H2O2 = 9.5 +/- 1.1 x 10(-7) M) but markedly increased the maximal rate of transport (Vmax control = 36.1 +/- 4.8 pmol/10(8) platelets/4 min versus Vmax H2O2 = 79.9 +/- 9.1 pmol/10(8) platelets/4 min). Washed platelets failed to be stimulated by H2O2; however, the addition of small amounts of plasma to the buffer medium fully restored the stimulating response to H2O2. These data suggest that a plasma factor regulates the active transport of 5-HT by platelets that are oxidatively stressed.
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PMID:Oxidant stress stimulates active transport of serotonin by platelets. 253 34

This work tested the hypotheses that splanchnic oxidant generation is important in determining heat tolerance and that inappropriate.NO production may be involved in circulatory dysfunction with heat stroke. We monitored colonic temperature (T(c)), heart rate, mean arterial pressure, and splanchnic blood flow (SBF) in anesthetized rats exposed to 40 degrees C ambient temperature. Heating rate, heating time, and thermal load determined heat tolerance. Portal blood was regularly collected for determination of radical and endotoxin content. Elevating T(c) from 37 to 41.5 degrees C reduced SBF by 40% and stimulated production of the radicals ceruloplasmin, semiquinone, and penta-coordinate iron(II) nitrosyl-heme (heme-.NO). Portal endotoxin concentration rose from 28 to 59 pg/ml (P < 0.05). Compared with heat stress alone, heat plus treatment with the nitric oxide synthase (NOS) antagonist N(omega)-nitro-L-arginine methyl ester (L-NAME) dose dependently depressed heme-.NO production and increased ceruloplasmin and semiquinone levels. L-NAME also significantly reduced lowered SBF, increased portal endotoxin concentration, and reduced heat tolerance (P < 0.05). The NOS II and diamine oxidase antagonist aminoguanidine, the superoxide anion scavenger superoxide dismutase, and the xanthine oxidase antagonist allopurinol slowed the rates of heme-.NO production, decreased ceruloplasmin and semiquinone levels, and preserved SBF. However, only aminoguanidine and allopurinol improved heat tolerance, and only allpourinol eliminated the rise in portal endotoxin content. We conclude that hyperthermia stimulates xanthine oxidase production of reactive oxygen species that activate metals and limit heat tolerance by promoting circulatory and intestinal barrier dysfunction. In addition, intact NOS activity is required for normal stress tolerance, whereas overproduction of.NO may contribute to the nonprogrammed splanchnic dilation that precedes vascular collapse with heat stroke.
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PMID:Mechanisms of circulatory and intestinal barrier dysfunction during whole body hyperthermia. 1115 46

This study aimed to investigate the effects of reactive oxygen species on the hepatic macrophages, the Kupffer cells (KC), and to identify the relevant targets of vasoconstrictors involved in the regulation of intrahepatic microcirculation and therefore portal pressure. The effects of hydrogen peroxide (H2O2), xanthine/xanthine oxidase or a thromboxane (TX) analogue (U46619; 0.1 microM) were tested in sham-operated and fibrotic livers (bile duct ligation over 4 weeks) during isolated rat liver perfusion and in vivo with or without additional KC blockade (gadolinium chloride, 10 mg kg(-1) body weight, 48 and 24 h, i.p.). To investigate downstream mechanisms, a TXA2 antagonist (BM 13.177; 20 microM) or a Rho kinase inhibitor (Y27632; 10 microM) was infused additionally. TXB2 efflux was measured by enzyme-linked immunosorbent assay. The phosphorylation state of moesin (p-moesin), as indicator for Rho kinase activity, was assessed by Western blot analyses. Portal pressure was dose-dependently increased by H2O2 (maximum, 0.5 mM) and, to a lower extent, by xanthine/xanthine oxidase together with catalase. The portal pressure increase by H2O2 was attenuated by previous KC blockade. TXA2 efflux increased after H2O2 infusion and was reduced by KC blockade. The TXA2 antagonist counteracted the H2O2-induced increase in portal pressure. The Rho kinase inhibitor attenuated portal pressure increase after TXA2 analogue or H2O2 infusion. Hepatic levels of p-moesin were increased after H2O2 infusion. Reactive oxygen species increased portal pressure via stimulation of TXA2 production by KCs and a subsequent Rho kinase-dependent contraction of the intrahepatic vasculature. In conclusion, the KCs that are well known to produce H2O2 could also be activated by H2O2. This vicious cycle may best be interrupted at the earliest time point.
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PMID:Kupffer cell activation by hydrogen peroxide: a new mechanism of portal pressure increase. 2011 78