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 vivo most extracellular iron is bound to transferrin or lactoferrin in such a way as to be unable to catalyze the formation of hydroxyl radical from superoxide (.O2-) and hydrogen peroxide (H2O2). At sites of Pseudomonas aeruginosa infection bacterial and neutrophil products could possibly modify transferrin and/or lactoferrin forming catalytic iron complexes. To examine this possibility, diferrictransferrin and diferriclactoferrin which had been incubated with pseudomonas elastase, pseudomonas alkaline protease, human neutrophil elastase, trypsin, or the myeloperoxidase product HOCl were added to a hypoxanthine/xanthine oxidase .O2-/H2O2 generating system. Hydroxyl radical formation was only detected with pseudomonas elastase treated diferrictransferrin and, to a much lesser extent, diferriclactoferrin. This effect was enhanced by the combination of pseudomonas elastase with other proteases, most prominently neutrophil elastase. Addition of pseudomonas elastase-treated diferrictransferrin to stimulated neutrophils also resulted in hydroxyl radical generation. Incubation of pseudomonas elastase with transferrin which had been selectively iron loaded at either the NH2- or COOH-terminal binding site yielded iron chelates with similar efficacy for hydroxyl radical catalysis. Pseudomonas elastase and HOCl treatment also decreased the ability of apotransferrin to inhibit hydroxyl radical formation by a Fe-NTA supplemented hypoxanthine/xanthine oxidase system. However, apotransferrin could be protected from the effects of HOCl if bicarbonate anion was present during the incubation. Apolactoferrin inhibition of hydroxyl radical generation was unaffected by any of the four proteases or HOCl. Alteration of transferrin by enzymes and oxidants present at sites of pseudomonas and other bacterial infections may increase the potential for local hydroxyl radical generation thereby contributing to tissue injury.
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PMID:Pseudomonas and neutrophil products modify transferrin and lactoferrin to create conditions that favor hydroxyl radical formation. 165 25

The effects of human neutrophil elastase (HNE), cathepsin-G, H2O2, xanthine oxidase-hypoxanthine derived superoxide anion and endotoxin on the PGI2 production by cultured bovine pulmonary endothelial cells were observed. The results showed that HNE, superoxide anion and H2O2 could decrease the PGI2 production by endothelial cells, and cathepsin-G had no effect on the production of PGI2. In our experiment, endotoxin could enhance PGI2 production. It was suggested that HNE, superoxide anion, and H2O2 may be involved in the pathogenesis of pulmonary hypertension.
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PMID:[Effect of human neutrophil elastase, cathepsin--G. superoxide anion and endotoxin on the PGI2 production by cultured bovine pulmonary endothelial cells]. 180 32

Using organ perfusing methods, the effect of activated neutrophils on pulmonary arterial pressure was examined. Lung of the rats were perfused with warm (37 degrees C) Krebs solution in constant flow rate. Perfusing pressure was obviously increased when adding activated PMN to the perfusate and permeability of pulmonary capillaries increased too. Elastase and oxygen free radical (OFR) were released by activated PMN. Human neutrophil elastase (HNE) and oxygen free radical produced from the reaction between xanthine and xanthine oxidase could inhibit PGI2 production by cultured bovine pulmonary arterial endothelial cells. OFR increased the tension of rabbit pulmonary arterial ring, and this effect was independent on endothelial cells. Results suggested that activated neutrophils and products released by them could directly cause the constriction of pulmonary arterial smooth muscle or inhibit PGI2 production which would increase the tension of pulmonary vessels. All this may play role in pathogenesis of pulmonary hypertension.
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PMID:[Effect of products released by activated neutrophils on pulmonary arterial pressure]. 208 53

The endothelial cells of pulmonary blood vessel play an significant role in lung vessel permeability, especially in acute lung damage and adult respiratory distress syndrome. In this study, bovine pulmonary endothelial cells were isolated, cultured and identified by means of reverse microscopic, scanning electromicroscopic, transmission electro- microscopic and immunofluorescence microscopic observation. Then they were labeled with 51Cr. Hydrogen peroxide (H2O2), H2O2 with catalase, xanthine oxidase (XO) with hypoxanthine (HX), human neutrophil elastase (HNE), cathepsin-G (C-G) and endotoxin (ET) were incubated with the labeled cells for half hour in various experimental groups respectively. The amount of 51Cr in the suspension released from the damaged cells was counted with r-radiometer. The results show that HNE, ET, H2O2 and superoxide anion (the latter is produced from the reaction between XO and HX) could at some degree damage the membrane of endothelial cells, and the inflammatory mediators of human neutrophils might play an important role in the development of pulmonary edema.
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PMID:[Effect of the products released from the activated human neutrophils and endotoxin on bovine pulmonary endothelial cells]. 208 56

Inherited or "acquired" deficiency of alpha 1-antitrypsin (believed to be the cause of pulmonary emphysema) will probably be treated in the future by replacement with alpha 1-antitrypsin purified from human plasma or produced by recombinant DNA, which seems promising because it permits site-specific mutagenesis in the oxidizable active site of the normal human alpha 1-antitrypsin. The aim of this in-vitro study was to investigate the elastase inhibitory activity and the resistance to oxidizing agents of normal human alpha 1-antitrypsin, a recombinant yeast-produced variant (VAL 358) and a recombinant E. coli-produced variant (LEU 358). The inhibitors were exposed to chemical oxidants (NCS, H2O2, xanthine/xanthine oxidase, chloramine-T) and to PMA-activated neutrophils. The elastase inhibitory activity was assayed on porcine pancreatic elastase and neutrophil elastase. Normal alpha 1-antitrypsin and VAL 358 variant were good inhibitors of both elastases. LEU 358 variant was the best inhibitor for neutrophil elastase, but it poorly inhibited the porcine pancreatic elastase. Normal alpha 1-antitrypsin was affected by all oxidants; both variants were almost totally resistant to chemical oxidants and to activated neutrophils. We conclude that recombinant alpha 1-antitrypsin variants differ in their elastase inhibitory activity and offer increased resistance to oxidant agents.
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PMID:Alpha 1-antitrypsin variants produced by recombinant DNA: differences in elastase inhibitory activity and resistance to oxidant agents. 210 1

Xanthine oxidase (XO)-generated toxic O2 metabolites appear to contribute to reperfusion injury, but the possibility that XO is involved in hyperoxic or neutrophil elastase-mediated injury has not been investigated. We found that lungs isolated from rats fed a tungsten-rich diet had negligible XO activities and after exposure to hyperoxia developed less acute edematous injury during perfusion with buffer or purified neutrophil elastase than XO-replete lungs from control rats which had been exposed to hyperoxia. In parallel, tungsten-treated XO-depleted cultured bovine pulmonary arterial endothelial cells made less superoxide anion and as monolayers leaked less 125I-labeled albumin after exposure to neutrophil elastase than XO-replete endothelial cell monolayers. Our findings suggest that XO-derived O2 metabolites contribute to acute edematous lung injury from hyperoxia directly and by enhancing susceptibility to neutrophil elastase.
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PMID:Xanthine oxidase mediates elastase-induced injury to isolated lungs and endothelium. 282 85

We have demonstrated that the endothelial cell-derived superoxide anion is deeply involved in the endothelial cell injury induced by activated neutrophils (Fujita, H., Morita, I. and Murota, S. (1994) Arch. Biochem. Biophys. 309, 62-69). To clarify the mechanism underlying the increase in the endothelial cell-derived superoxide anion induced by activated neutrophils, the conversion of xanthine dehydrogenase (XD) to xanthine oxidase (XO) in cultured endothelial cells isolated from bovine carotid arteries was investigated. Although the endothelial cells expressed both XD and XO activity, the XO activity of unstimulated cells comprised about 12% of the total (XD + XO) activity. When endothelial cells were exposed to neutrophils activated with phorbol 12-myristate 13-acetate (PMA), XO activity rapidly increased about 3-fold over the control. Whereas treatment of endothelial cells with PMA alone or unstimulated neutrophils alone did not increase the XO activity at all. The increase in XO activity in endothelial cells was also observed on the treatment of the cells with neutrophils activated with leukotriene B4 or thrombin. To determine whether or not proteases released from activated neutrophils are involved in the increased conversion of XD to XO in endothelial cells, the effects of the elastase specific inhibitor, ONO-5046, and protease inhibitors, such as aprotinin, gabexate mesylate and urinastatin, were examined. However, these protease inhibitors did not suppress the conversion of XD to XO induced by PMA-activated neutrophils. Moreover, the treatment of endothelial cells with purified human neutrophil elastase and H2O2 also did not affect the conversion at all. In contrast, monoclonal antibodies against CD11a and CD18 significantly inhibited the increased conversion of XD to XO induced by PMA-activated neutrophils. Moreover, tyrosine kinase inhibitors such as staurosporin and herbimysine also inhibited the increased conversion of XD to XO induced by PMA-activated neutrophils. These results indicate that the adhesion of activated neutrophils to endothelial cells via CD11a/CD18-ICAM-1 is involved in the conversion of XD to XO in endothelial cells induced by activated neutrophils.
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PMID:Conversion of xanthine dehydrogenase to xanthine oxidase in bovine carotid artery endothelial cells induced by activated neutrophils: involvement of adhesion molecules. 769 38

Reactive oxygen species have been shown to play an important role in the pathogenesis of lung injury. This study was designed to clarify the role of intrapulmonary neutrophils in the development of xanthine/xanthine oxidase (X/XO)-induced lung injury in isolated buffer-perfused rabbit lungs. We measured microvascular fluid filtration coefficient (K(f)) and wet-to-dry weight ratio to assess lung injury. X/XO induced a significant increase in K(f) and wet-to-dry weight ratio in neutrophil-replete lungs, whereas the lung injury was attenuated in neutrophil-depleted lungs. A neutrophil elastase inhibitor, ONO-5046, also attenuated the lung injury. In addition, X/XO induced a transient pulmonary arterial pressure (P(pa)) increase. The thromboxane inhibitor OKY-046 attenuated the P(pa) increase but did not alter the increase in permeability. Neutrophil depletion reduced the K(f) increase but had no effect on the P(pa) increase. These results suggest that intrapulmonary neutrophils activated by X/XO play a major role in development of the lung injury, that neutrophil elastase is involved in the injury, and that the X/XO-induced vasoconstriction is independent of intrapulmonary neutrophils.
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PMID:Role of neutrophils in xanthine/xanthine oxidase-induced oxidant injury in isolated rabbit lungs. 1060 Nov 84

Alpha(1)-proteinase inhibitor (alpha(1)-PI) is a natural serine protease inhibitor. Although mainly thought to protect the airways from neutrophil elastase, alpha(1)-PI may also regulate the development of airway hyperresponsiveness (AHR), as indicated by our previous findings of an inverse relationship between lung alpha(1)-PI activity and the severity of antigen-induced AHR. Because allergic stimulation of the airways causes release of elastase, tissue kallikrein, and reactive oxygen species (ROS), all of which can reduce alpha(1)-PI activity and contribute to AHR, we hypothesized that administration of exogenous alpha(1)-PI should protect against pathophysiological airway responses caused by these agents. In untreated allergic sheep, airway challenge with elastase, xanthine/xanthine oxidase (which generates ROS), high-molecular-weight kininogen, the substrate for tissue kallikrein, and antigen resulted in bronchoconstriction. ROS and antigen also induced AHR to inhaled carbachol. Treatment with 10 mg of recombinant alpha(1)-PI (ralpha(1)-PI) blocked the bronchoconstriction caused by elastase, high-molecular-weight kininogen, and ROS, and the AHR induced by ROS and antigen. One milligram of ralpha(1)-PI was ineffective. These are the first in vivo data demonstrating the effects of ralpha(1)-PI. Our results are consistent with and extend findings obtained with human plasma-derived alpha(1)-PI and suggest that alpha(1)-PI may be important in the regulation of airway responsiveness.
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PMID:Recombinant alpha 1-proteinase inhibitor blocks antigen- and mediator-induced airway responses in sheep. 1243 33

The inhibition of the proliferation rate of the immortalized human cell line ECV 304 after oxidant damage by oxygen radicals generated in a hypoxanthin-xanthine oxidase system and the protection provided by various propolis extracts was determined. Best inhibition was demonstrated by 60-80% ethanolic extracts (IC50 of approximately 2 microg dry weight/ml) and by the ethyl acetate extract (IC50 of 6.9 microg dry weight/ml). The beneficial effect of polar extracts was quite weak. Human neutrophil elastase activity was inhibited distinctively by ethanolic (60 to 96%) and ethyl acetate extracts (IC50 of approximately 2 microg dry weight/ml). Both activities seem to be responsible for the anti-inflammatory effect of the extract.
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PMID:Effects of propolis on hypoxanthine-xanthine oxidase-induced toxicity in cultivated human cells and on neutrophil elastase activity. 1599 94


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