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)

Xanthine oxidase has been implicated in the production of reactive oxygen species and cell injury produced by various toxic compounds. Since allyl alcohol injuries the liver by an oxygen-dependent mechanism, we examined the actions of this hepatotoxicant on the conversion of xanthine dehydrogenase into xanthine oxidase in perfused livers. A microassay for NAD(+)-dependent xanthine dehydrogenase, based on measuring the production of NADH fluorometrically under anaerobic conditions, was developed and used to examine the actions of allyl alcohol on this activity in periportal and pericentral regions of the liver lobule. The oxygen-dependent activity, xanthine oxidase, was monitored in whole liver homogenates by uric acid formation at 302 nm under aerobic conditions. Perfusion of the liver with allyl alcohol (350 microM) increased xanthine oxidase and decreased xanthine dehydrogenase in whole liver consistent with the hypothesis that allyl alcohol enhanced calcium-dependent proteolytic conversion of the NAD(+)-dependent to the O2-dependent form. Xanthine dehydrogenase was higher in pericentral than in periportal regions of the liver lobule and tended to decrease selectively in periportal zones of livers exposed to allyl alcohol. O2 uptake was stimulated transiently by allyl alcohol followed by subsequent inhibition of respiration. These results are consistent with the idea that conversion of NAD(+)-dependent xanthine dehydrogenase to xanthine oxidase is involved in the zone-specific hepatotoxicity of allyl alcohol.
Toxicol Lett 1991 Sep
PMID:Effect of allyl alcohol on xanthine dehydrogenase activity in the perfused rat liver. 189 1

The potential role of oxidative stress conditions in the induction of heat shock proteins was studied in human umbilical vein endothelial cells. We compared the effects of temperature (43 to 45 degrees C), exposure to hydrogen peroxide (H2O2) and oxygen metabolites generated by the enzyme system hypoxanthine-xanthine oxidase (O2- plus H2O2), as well as exposure to 95% O2, on the expression of the major 70-kD heat shock proteins (hsp70). Northern blot analysis indicated that: (1) heat shock induced a rapid and marked increase in hsp70 mRNA levels that reached a maximum during recovery from a 30-min exposure to 45 degrees C; (2) treatment with a 5-mM H2O2 bolus or 50 mU/ml xanthine oxidase also increased hsp70 mRNA levels but to a lesser extent than heat shock (about 10 and 25 times less, respectively); (3) no change was detected after a 5-day exposure to 95% O2. Nuclear run on transcription data and kinetics of mRNA decay in the presence of actinomycin D indicated that the observed increase in hsp70 mRNA levels in both heat-shocked and H2O2-treated cells was mainly due to a transcriptional induction. The kinetics of hsp70 synthesis correlated with the accumulation of hsp70 mRNA. Two-dimensional gel electrophoresis and immunologic analysis of these heat shock proteins revealed a series of at least five distinct hsp70 isoforms induced in heat-shocked cells, whereas only a specific subset of these proteins, mainly one acidic isoform, was induced in very low amounts in response to H2O2 treatment. These results clearly indicate that the endothelial cell responses to oxidative stress and heat shock differ in both qualitative and quantitative terms in respect to hsp70 induction. They also suggest that the intensity of this response to oxidative stress conditions may vary depending on the nature of the oxidative challenge.
Am J Respir Cell Mol Biol 1991 Sep
PMID:Differential expression of hsp70 stress proteins in human endothelial cells exposed to heat shock and hydrogen peroxide. 191 Aug 12

Clinical evidence has suggested that mitomycin C (MMC) potentiates doxorubicin (DOX) induced cardiotoxicity. In this study a mouse model was used to examine the effect of DOX on the ability of cardiac tissue to bioactivate MMC to generate oxygen radicals. Cardiac damage was assessed by measuring serum CPK-MB isoenzyme levels and thiobarbituric acid reactive substances (TBARS) in the cardiac tissue. The exposure of animals to DOX or DOX and MMC over a three week period led to an increase in serum CPK-MB isoenzyme levels as well as TBARS. Treatment with DOX led to an increase in MMC-dependent, NADH-dependent, cyanide insensitive oxygen consumption, compared to control animals, thereby suggesting increased MMC-dependent oxygen radical generation. Levels of xanthine oxidase (XO; EC 1.1.3.22) and NADPH:cytochrome C reductase, two enzymes known to bioactivate MMC with subsequent oxygen radical generation, were measured in cardiac tissue with a 4.5 x increase in XO activity seen in DOX treated animals vs controls and no change in NADPH:cytochrome C reductase activity. Cardiac levels of xanthine dehydrogenase (XDH; EC 1.1.1.204) activity in DOX treated animals decreased while the XO/XDH ratio increased, suggesting a conversion of XDH to XO following DOX treatment.
Cancer Commun 1991 Sep
PMID:Role of xanthine oxidase in the potentiation of doxorubicin-induced cardiotoxicity by mitomycin C. 191 Oct 46

Alteration in oxidant-antioxidant balance is a key feature of many common vascular diseases. Using an isolated perfused heart model, we found that (a) xanthine oxidase-derived oxygen radicals contributed to ischemia-reperfusion injury; (b) addition of antioxidants within or outside erythrocytes decreased injury following ischemia-reperfusion; (c) endotoxin pretreatment increased myocardial catalase activity and decreased injury following ischemia-reperfusion; (d) interleukin pretreatment increased myocardial glucose-6-phosphate activity and decreased ischemia-reperfusion injury, and (e) neutrophils mediated tolerance to a subsequent oxidative stress by causing a small oxidant stress that in turn increased antioxidant protection mechanisms.
Am J Med 1991 Sep 30
PMID:Oxidant-antioxidant balance: some observations from studies of ischemia-reperfusion in isolated perfused rat hearts. 192 11

Interactions between rat pulmonary artery endothelial cells and hydrogen peroxide or toxic oxygen products from phorbol ester-activated human neutrophils result in endothelial cell killing defined by 51Cr release. It has been shown that this cytotoxic reaction can be blocked by the presence of catalase, iron chelators, or scavengers of the hydroxyl radical. Evidence shows that products from xanthine oxidase of endothelial cells are necessary for the toxic effects of hydrogen peroxide or phorbol ester-activated neutrophils. Addition of xanthine oxidase inhibitors protects against phorbol ester-mediated injury of endothelial cells. Preloading of endothelial cells with superoxide dismutase attenuates injury caused either by hydrogen peroxide or phorbol ester-activated neutrophils. Conversion of xanthine dehydrogenase to xanthine oxidase in endothelial cells occurs during contact of endothelial cells by activated neutrophils. This conversion is not related to oxygen products of neutrophils. Conversion of xanthine dehydrogenase to xanthine oxidase in endothelial cells is also induced by endothelial cell contact with C5a, N'-formyl-methionyl-leucyl-phenylalanine (fMLP), or tumor necrosis factor alpha (TNF alpha). Interaction of hydrogen peroxide with endothelial cells rapidly depletes adenosine triphosphate (ATP) and causes the extracellular appearance of xanthine and hypoxanthine. Agents that protect endothelial cells from the toxic effects of hydrogen peroxide do not prevent falls in cellular ATP caused by hydrogen peroxide, indicating that ATP levels do not necessarily correlate with cytotoxic events. A synergy between hydrogen peroxide and proteases in endothelial cell killing has been demonstrated. TNF alpha causes alterations in endothelial cells, the result of which is increased susceptibility to killing by PMA-activated neutrophils.
Am J Med 1991 Sep 30
PMID:Mechanisms of endothelial cell killing by H2O2 or products of activated neutrophils. 192 18

Circulating antibodies to whole dried cows' milk, previously reported to be elevated in patients with myocardial infarction, have been shown to be directed mainly to the bovine milk fat globule membrane. Human antibodies against the bovine milk fat globule membrane themselves interact primarily with the enzyme, xanthine oxidase. Comparison of anti-(xanthine oxidase) antibody levels in 107 patients, who had suffered a myocardial infarction, with those in 86 control subjects showed significantly higher IgM levels in the patients with myocardial infarction. No corresponding differences were found for IgG or IgA anti-(xanthine oxidase) antibodies. Total levels of IgM class immunoglobulins did not differ between patients and controls. Serial assays following myocardial infarction showed no evidence that raised levels of IgM anti-(xanthine oxidase) antibodies result from the infarction itself.
Cardioscience 1990 Sep
PMID:Antibodies to xanthine oxidase: elevated levels in patients with acute myocardial infarction. 210 7

Damage to the bases in DNA by the cupric ion-1,10-phenanthroline complex was investigated. Ten base products in DNA were identified and quantitated by the use of gas chromatography/mass spectrometry with selected-ion monitoring. DNA damage by the cupric ion-1,10-phenanthroline complex required the presence of a reducing agent such as ascorbic acid or mercaptoethanol. Products identified were typical hydroxyl radical induced products from the pyrimidines and purines in DNA, well-known from previous studies using various hydroxyl radical producing systems such as ionizing radiation, hypoxanthine/xanthine oxidase, or hydrogen peroxide in the presence of transition metal ions. Product formation was not significantly inhibited by typical scavengers of hydroxyl radical such as mannitol and sodium formate, but there was partial inhibition by dimethyl sulfoxide. Catalase substantially decreased formation of base products, and added hydrogen peroxide stimulated it, indicating the hydrogen peroxide dependency of DNA base damage. Superoxide dismutase afforded only a partial reduction in product yields in systems containing ascorbic acid. On the basis of the types of base products formed, the hydrogen peroxide dependency of product formation, and a previous report suggesting that DNA damage is due to a diffusible species [Williams, L. D., Thivierge, J., & Goldberg, I. H. (1988) Nucleic Acids Res. 16, 11607-11615], we propose that DNA base damage is caused by hydroxyl radical.
Biochemistry 1990 Sep 11
PMID:Modification of bases in DNA by copper ion-1,10-phenanthroline complexes. 212 17

Ventricular myocytes from neonatal Wistar rats were cultured with 80% Dulbecoo's modified Eagle medium and 20% fetal bovine serum. An appropriate amount of xanthine and xanthine oxidase was added to the culture medium to increase the content of free radicals in cardiac cells. Variation in action potential and input impedance of cardiac myocytes indicated the oxidative damage to the membrane. The ultrastructure of heart cells, characteristically the myofilaments and mitochondria, was damaged. Electron spin resonance measurement demonstrated that xanthine and xanthine oxidase elevated the free radical content, while selenium (Se) and manganese (Mn) reduced the free radicals in cultured heart cells. Supplementation of 0.173 microgram/ml Se and 0.1 microgram/ml Mn into the culture medium separately or simultaneously antagonized the damage induced by xanthine and xanthine oxidase. The possible mechanism might be the production of superoxide anion free radical leading to free radical damage to cardiac cells. Se and Mn might play a role as scavengers through glutathione peroxidase and superoxide dismutase respectively and thus protect cardiac cells from free radical damage.
Chin Med J (Engl) 1990 Sep
PMID:Protective action of selenium and manganese on xanthine and xanthine oxidase induced oxidative damage to cultured heart cells. 212 74

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.
J Mol Cell Cardiol 1990 Sep
PMID:Free radicals alter ionic calcium levels and membrane phospholipids in cultured rat ventricular myocytes. 212 94

On the basis of recent reports that the proportion of linoleic acid (C18:2Cis 9,12), a free fatty acid, is markedly decreased in acne comedones and that tetracycline is effective against acne comedones by acting directly as an antioxidant on infiltrating neutrophils, we investigated the effect of linoleic acid on several inflammatory parameters of neutrophils, including neutrophil chemotaxis, phagocytosis, and generation of reactive oxygen species (ROS). Linoleic acid significantly decreased phagocytosis and the generation of O2-, H2O2, and OH.by neutrophils, whereas it did not significantly inhibit neutrophil chemotaxis or decrease the ROS levels generated in a cell-free, xanthine-xanthine oxidase system. The present study seems to suggest that decreased levels of linoleic acid in acne comedones contribute, in part, to the worsening of acne inflammation by the failure of low levels of linoleic acid to suppress neutrophil phagocytosis and ROS generation.
J Invest Dermatol 1990 Sep
PMID:Suppressive effects of linoleic acid on neutrophil oxygen metabolism and phagocytosis. 214 21


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