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)

Polymorphonuclear leukocytes secreting oxygen radicals are found in the glomerular capillaries at an early stage of experimental acute glomerulonephritis. The aim of this work was to study the effects of these radicals on prostaglandin (PG) production by the glomeruli. Glomeruli were isolated from rat renal cortex and incubated in the presence of a biochemical system capable of generating oxygen radicals (addition to 100 microM xanthine of increasing concentrations of xanthine oxidase). Synthesis of PGE2, PGF2alpha, 6 keto PGF1alpha, and TXB2 estimated using specific radioimmunoassays was twofold greater in the presence of oxygen radicals. This effect was inhibited by catalase, slightly stimulated by superoxide dismutase, unaffected by hydroxyl radical scavengers, thus suggesting that hydrogen peroxide was the by-product responsible. This was confirmed by the stimulatory effect of hydrogen peroxide itself (1 to 100 microM) on PG synthesis. The effect of mepacrine, an inhibitor of phospholipase activity, on PG production was more marked in the presence of hydrogen peroxide and the stimulation of PG synthesis by hydrogen peroxide or oxygen radicals was progressively inhibited in the presence of arachidonic acid. Moreover, oxygen radicals stimulated the release of 14C-arachidonic acid previously incorporated in isolated glomeruli. This demonstrates that the increase in PG synthesis in response to oxygen radicals is due to activation of glomerular phospholipase by these radicals. This effect that is likely to occur at an early stage of experimental glomerulonephritis could play a role in the mechanism of the inflammatory process.
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PMID:Stimulation by oxygen radicals of prostaglandin production by rat renal glomeruli. 730 Jan 22

There is considerable evidence suggesting that reactive oxygen species (ROS) are implicated in the pathogenesis of ischemic, toxic, and immunologically-mediated renal injury. In experimental renal ischemia, ROS sources include the electron transport chain, oxidant enzymes (xanthine oxidase), phagocytes, and auto-oxidation of epinephrine. ROS cause lipid peroxidation of cell and organelle membranes and, hence, disruption of the structural integrity and capacity for cell transport and energy production, especially in the proximal tubule segment. In experimental immune glomerulonephritis, ROS are generated by both infiltrating blood-borne cells (polymorphonuclear leukocytes and monocytes) and resident glomerular cells, mainly mesangial cells. Their formation results in morphologic lesions and in modifications of glomerular permeability to proteins through activation of proteases and reduction of proteoglycan synthesis. Additionally, they promote a reduction in glomerular blood flow and glomerular filtration rate through liberation of vasoconstrictory bioactive lipids (prostaglandins, thromboxane, and platelet activating factor) and, possibly, inactivation of relaxing nitric oxide. Further studies are needed to address the role of ROS in human glomerular diseases.
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PMID:Involvement of reactive oxygen species in kidney damage. 822 Oct 27

Reactive oxygen radicals generated by mesangial cells or by resident or infiltrating macrophages may contribute to glomerular injury in glomerulonephritis. To determine whether superoxide anions have an effect on the glomerular barrier to macromolecules, we studied the responses of isolated glomeruli after exposure to superoxide generated by xanthine and xanthine oxidase or by activated macrophages. Glomerular volumetric responses to oncotic gradients of bovine serum albumin or an impermeant neutral dextran (mol wt 252 kd0 were used to calculate the albumin reflection coefficient (sigma albumin) and convectional permeability to albumin (1-sigma albumin) of control and superoxide-treated glomeruli. Albumin permeability of control glomeruli was not different from 0 (0.02 +/- 0.01, N = 50). After 10 minutes of exposure of glomeruli to superoxide generated by xanthine oxidase, albumin permeability was increased to 0.06 +/- 0.01 (N = 50). Albumin permeability did not increase further after incubations with xanthine and xanthine oxidase for up to 60 minutes. The increase in albumin permeability was prevented by superoxide dismutase (-0.02 +/- 0.01, N = 48) but was not affected by catalase or by indomethacin pretreatment. Coincubation of glomeruli with activated macrophages also increased albumin permeability to a maximum of 0.80 +/- 0.05 (N = 17). Albumin permeability was not increased by incubation of glomeruli with phorbol myristate acetate alone or with macrophages in the absence of phorbol myristate acetate. The effect of activated macrophages on albumin permeability, like that of superoxide generated chemically, was prevented by superoxide dismutase but not by catalase or indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of superoxide exposure on albumin permeability of isolated rat glomeruli. 838 94

Nitric oxide (NO.) and superoxide (O2-) are inflammatory mediators. Their formation seems to be associated with apoptotic and/or necrotic cell death in diseases such as mesangioproliferative glomerulonephritis in which the early phase of mesangiolysis is linked to significant NO. production. Notably, mesangial cells (MC) not only generate NO. but also O2- after cytokine stimulation. Here we investigated the interrelation between NO. and O2- in MC death by generating both radicals with the use of NO donors (S-nitrosoglutathione, spermine-NO) and O2(-)-generating systems (2,3-dimethoxy-1,4-naphtoquinone, hypoxanthine/xanthine oxidase). Exogenously supplied NO. or O2- in a concentration-dependent manner induced apoptosis and/or necrosis. Apoptosis is characterized by chromatin condensation and DNA fragmentation in contrast to necrotic cytoplasmatic membrane rupture. Noteworthy, coincubation of NO. and O2- was cross-protective. Maximum protection required the existence of a balanced NO./O2- ratio. Analysis in cytokine-stimulated MC suggests endogenous radical formation, which may participate in modulating apoptosis. Manipulation of the endogenous NO./O2- ratio by exogenous, sublethal S-nitrosoglutathione in addition to cytokines produced death, which was antagonized by inducible nitric oxide synthase (iNOS) inhibition. Moreover, pyrrolidine dithiocarbamate supplementation, which down-regulates iNOS expression and blocks superoxide dismutase activity, initiates apoptosis. Our results imply the participation of reactive nitrogen and oxygen species in determining life and death of MC.
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PMID:The balance between nitric oxide and superoxide determines apoptotic and necrotic death of rat mesangial cells. 914 12

Increased mesangial cell proliferation is a hallmark of many glomerulopathies in humans. Whereas the pathogenic role of reactive oxygen species (ROS) in the development of experimental mesangioproliferative glomerulonephritis (GN) is well established, very little is known about the mechanisms leading to increased ROS concentrations in the glomerulus. This study therefore examined glomerular ROS and the activities of oxidative and antioxidative enzymes during the early course of mesangioproliferative anti-Thy 1.1 GN. Anti-Thy 1.1 GN was induced in male Wistar rats, and glomeruli were isolated 2, 24, and 120 h after disease induction to examine ROS levels as well as oxidative and antioxidative enzyme expression in comparison to non-nephritic controls. At all time points, increased glomerular ROS levels, particularly of hydrogen peroxide and superoxide anions, were observed. Activities of NADH-dependent and NADPH-dependent oxidative enzymes were also increased during the course of GN, whereas no increased activity of xanthine oxidase, another potential source of ROS, was detectable. Despite glomerular oxidative stress, no compensatory increase of antioxidative enzyme activities occurred. On the contrary, catalase, superoxide dismutase, and glutathione peroxidase activities even decreased during the course of disease. In tubulointerstitial samples, no increase in oxidative activity was observed in the course of disease, thus confirming that detected ROS were of glomerular origin. Our data document for the first time a pronounced dysregulation of pro-oxidative and antioxidative enzymes in mesangioproliferative GN, leading to a net increase in glomerular ROS levels. Detailed knowledge of such pathways may lead to new therapeutic approaches for GN in humans.
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PMID:Glomerular oxidative and antioxidative systems in experimental mesangioproliferative glomerulonephritis. 1244 11

Nicorandil exhibits a protective effect in the vascular system, which is thought to be due to vasodilatation from opening ATP-dependent potassium channels and donation of nitric oxide. Recently, nicorandil was shown to be renoprotective in models of acute kidney injury and glomerulonephritis. However, the specific mechanisms of renoprotection are unclear. We evaluated the effect of nicorandil on the rat remnant kidney model of chronic kidney disease. Blood pressure was unchanged by a 10-wk course of nicorandil, while albuminuria was significantly reduced. Glomerular injury and tubulointerstitial injury were also ameliorated by nicorandil. Oxidative stress, as noted by renal nitrotyrosine level and urine 8-hydroxy-2'-deoxyguanosine, were elevated in this model and was significantly reduced by nicorandil treatment. Treatment was associated with maintenance of the mitochondrial antioxidant, manganese SOD, in podocytes and with suppression of xanthine oxidase expression in infiltrating macrophages. Interestingly, these two cell types express sulfonylurea receptor 2 (SUR2), a binding site of nicorandil in the ATP-dependent K channel. Consistently, we found that stimulating SUR2 with nicorandil prevented angiotensin II-mediated upregulation of xanthine oxidase in the cultured macrophage, while xanthine oxidase expression was rather induced by blocking SUR2 with glibenclamide. In conclusion, nicorandil reduces albuminuria and ameliorates renal injury by blocking oxidative stress in chronic kidney disease.
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PMID:Nicorandil, a K(atp) channel opener, alleviates chronic renal injury by targeting podocytes and macrophages. 2262 55