Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:1.17.3.2 (xanthine oxidase)
8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An experimental group of mice were subjected to a hindlimb tourniquet for 90 min followed by 60 min postischemic reperfusion (ischemia/reperfusion, I/R). Two further groups with the same experimental procedure received allopurinol to inhibit endothelial xanthine oxidase to produce oxygen free radicals (I/R-allo) or vitamin E as a radical scavenger (I/R-vitE). The soleus muscle was examined, and the contralateral muscle served as control. Glutathione (both reduced and oxidized forms, GSH and GSSG) concentrations and the relative protein content were measured. Additionally, the muscles were examined under the electron microscope for pathological alterations. The results showed: (i) the existence of much oxidative stress in the I/R group, but not in the I/R-allo and I/R-vitE groups; (ii) an increased protein content indicative for high capillary permeability in the I/R group, but not in the I/R-allo and I/R-vitE groups; (iii) considerably fewer capillary endothelial disturbances in the I/R-allo and I/R-vitE groups than in the I/R group. We conclude that allopurinol and vitamin E diminished the occurrence of oxidative stress and of edema in postischemic skeletal muscle.
...
PMID:Administration of tourniquet. II. Prevention of postischemic oxidative stress can reduce muscle edema. 900 76

Reactive oxygen metabolites produce colonic epithelial cellular injury. The present study evaluated the protective role of cellular superoxide dismutase, catalase, and glutathione (GSH) redox cycle in cultured rabbit colonic cells. Cultured rabbit colonic epithelial cells were exposed to reactive oxygen metabolites generated by hypoxanthine (1 mM) and xanthine oxidase (1 mU/ml) for up to 5 h. Cytotoxicity was quantified by measuring 51Cr release from prelabeled cells. Pretreatment with diethyldithiocarbamate (inhibitor of superoxide dismutase) reduced activity of cellular superoxide dismutase and increased 51Cr release caused by hypoxanthine/xanthine oxidase from colonic cells. Pretreatment with diethyl maleate (covalently binds GSH as catalyzed by GSH transferase), or buthionine sulfoximine (inhibitor of gamma-glutamylcysteine synthetase) decreased cellular GSH and enhanced reactive oxygen metabolites induced injury. Pretreatment with bis(chloroethyl)-nitrosourea (inhibitor of GSH reductase) inhibited activity of GSH reductase and increased 51Cr release from colonic cells. Preincubation with aminotriazole (inhibitor of catalase) reduced cellular catalase, but did not affect cellular injury. Therefore, we concluded that both cellular superoxide dismutase and the GSH redox cycle appeared to play a role in detoxifying reactive oxygen metabolites and that cellular catalase may be less important in rabbit colonic epithelial cells.
...
PMID:Antioxidant defenses of cultured colonic epithelial cells against reactive oxygen metabolites. 908 93

Dynemicin A (1), a member of the enediyne family of natural products, binds to double-stranded DNA (K(B) approximately 10(4) M(-1)) and in the presence of millimolar concentrations of a reducing cofactor such as NADPH or GSH reacts to cleave DNA. In this work, we show that the two flavin-based enzymes ferredoxin-NADP+ reductase and xanthine oxidase catalyze the reductive activation of 1 by NADPH and NADH, respectively. The enzyme-catalyzed reductive activation of 1 leads to more rapid and efficient cleavage of DNA, even with 10-20-fold lower concentrations of the stoichiometric reductant. Significantly, the enzymatic systems are also found to activate the tight-binding (K(B) > or = 10(6) M(-1)) synthetic dynemicin analogs 3 and 5 toward DNA cleavage. These same analogs do not undergo reductive activation with NADPH or NADH alone, where evidence has been obtained to support the proposal that the DNA-bound drugs are protected from reductive activation. The new enzymatic activation processes described may have important implications for chemistry occurring with 1 and synthetic analogs in vivo, as well as for the future development of dynemicin-based anticancer agents.
...
PMID:Enzymatic activation of DNA cleavage by dynemicin A and synthetic analogs. 909 20

Although the formation of oxygen-derived free radicals (or reactive oxygen species; ROS) and the release of endogenous opioid peptides (EOP) have been independently reported to be the major arrhythmogenic factors in ischemic hearts, possible relations between these two factors have seldom been investigated. Thus, we studied whether the ROS and EOP were related in the progression of ischemia-induced arrhythmias. Isolated rat hearts perfused in the Langendorff mode were treated with dynorphin A1-13 (kappa EOP receptor agonist), and/or allopurinol (xanthine oxidase inhibitor), before the onset of ischemia induced by ligating the left coronary arteries. Ischemic period lasted for 30 min, during which cardiac rhythms were recorded. At the end of ischemia, hearts were analyzed for the glutathione and ascorbate levels. Allopurinol (100 nmoles/heart) was effective in reducing the severity of arrhythmia (arrhythmia score: Mean +/- SEM 3.00 +/- 0.80 for allopurinol, 5.75 +/- 0.41 for placebo, p < 0.01), while dynorphin (10 micrograms/heart) potentiated the arrhythmia (6.71 +/- 0.52, p < 0.05 vs. placebo). Coadministration of allopurinol and dynorphin was capable of reducing arrhythmia (5.57 +/- 0.65) when compared with the administration of dynorphin alone (6.71 +/- 0.52, p < 0.05). Tissue oxidative stress was evaluated by the concentrations of glutathione (GSH) and ascorbate. Allopurinol did not significantly elevate tissue GSH concentrations (1.46 +/- 0.05 mumoles/g wet wt) in ischemic hearts, while dynorphin alone significantly decreased the GSH concentrations (0.96 +/- 0.08, p < 0.05) when compared with the placebo (1.32 +/- 0.03). The dynorphin-induced GSH decrease cannot be reversed by coadministration with allopurinol (0.90 +/- 0.104). Allopurinol significantly elevated tissue ascorbate levels (0.16 +/- 0.01) when compared with placebo (0.10 +/- 0.01, p < 0.05). Interestingly, dynorphin alone also elevated the tissue ascorbate concentrations (0.16 +/- 0.02). Coadministration of allopurinol and dynorphin further spiked the ascorbate levels (0.28 +/- 0.05, p < 0.01). In conclusion, the results suggested that ischemia-induced arrhythmia mechanisms might involve the formation of superoxide and other ROS, which were probably generated from the release of EOP (or EOP/EOP receptor interactions). Superoxide, the formation of which can be inhibited by allopurinol that exerted antiarrhythmic effect, was probably scavenged by ascorbate in myocardial ischemia. The ROS resulting from EOP/EOP receptor interactions were probably scavenged by glutathione system. Elevated ascorbate levels in dynorphin-treated hearts might result from the compensatory synthesis induced by decreased glutathione levels.
...
PMID:The roles of reactive oxygen species and endogenous opioid peptides in ischemia-induced arrhythmia of isolated rat hearts. 910 Dec 52

Thiol-containing proteins are key to numerous cellular processes, and their functions can be modified by thiol nitrosation or oxidation. Nitrosation reactions are quenched by O-2, while the oxidation chemistry mediated by peroxynitrite is quenched by excess flux of either NO or O-2. A solution of glutathione (GSH), a model thiol-containing tripeptide, exclusively yielded S-nitrosoglutathione when exposed to the NO donor, Et2NN(O)NONa. However, when xanthine oxidase was added to the same mixture, the yield of S-nitrosoglutathione dramatically decreased as the activity of xanthine oxidase increased, such that there was a 95% reduction in nitrosation when the fluxes of NO and O-2 were nearly equivalent. The presence of superoxide dismutase reversed O-2-mediated inhibition, while catalase had no effect. Increasing the flux of O-2 yielded oxidized glutathione (GSSG), peaking when the flux of NO and O-2 were approximately equivalent. The results suggest that oxidation and nitrosation of thiols by superoxide and NO are determined by their relative fluxes and may have physiological significance.
...
PMID:Superoxide modulates the oxidation and nitrosation of thiols by nitric oxide-derived reactive intermediates. Chemical aspects involved in the balance between oxidative and nitrosative stress. 911 Oct 12

The protein, NKEF (natural killer enhancing factor), has been identified as a member of an antioxidant family of proteins capable of protecting against protein oxidation in cell-free assay systems. The mechanism of action for this family of proteins appears to involve scavenging or suppressing formation of protein thiyl radicals. In the present study we investigated the antioxidant protective properties of the NKEF-B protein overexpressed in an endothelial cell line (ECV304). Nkef-B-transfected cells displayed significantly lower levels of reactive oxygen species (ROS) compared with control or vector-transfected cells. Tert-Butylhydroperoxide-induced ROS was 15% lower in nkef-B-transfected cells and cytotoxicity was slightly, though not significantly, lower. NKEF-B had no effect on ROS induced by menadione or xanthine plus xanthine oxidase. NKEF-B overexpression resulted in slightly (approximately 10%) lower levels of cellular glutathione (GSH) and had no effect on rate or extent of GSH depletion following either diethylmaleate (DEM) or buthionine sulfoximine (BSO) treatment. Lipid peroxidation, assessed as thiobarbituric acid-reactive substances, was 40% lower in nkef-B-transfected cells compared with vector-only-transfected cells. DEM-induced lipid peroxidation was suppressed by NKEF-B at DEM concentrations of 20 microM to 1 mM. At 10 mM DEM, lipid peroxidation was unaffected by NKEF-B. NKEF-B expression also protected cells against menadione-induced inhibition of [3H]-thymidine uptake. The NKEF-B protein appears most effective in suppressing basal low-level oxidative injury such as that produced during normal metabolism. These results indicate that overexpression of the NKEF-B protein promotes resistance to oxidative stress in this endothelial cell line.
...
PMID:Cellular antioxidant properties of human natural killer enhancing factor B. 916 49

Previously, our laboratory reported that lactosylceramide (LacCer) stimulated human aortic smooth muscle cell proliferation via specific activation of p44 mitogen-activated protein kinase (MAPK) in the p21(ras)/Raf-1/MEK2 pathway and induced expression of the transcription factor c-fos downstream to the p44 MAPK signaling cascade (Bhunia A. K., Han, H., Snowden, A., and Chatterjee S. (1996) J. Biol. Chem. 271, 10660-10666). In the present study, we explored the role of free oxygen radicals in LacCer-mediated induction of cell proliferation. Superoxide levels were measured by the lucigenin chemiluminescence method, MAPK activity was measured by immunocomplex kinase assays, and Western blot analysis and c-fos expression were measured by Northern blot assay. We found that LacCer (10 microM) stimulates endogenous superoxide production (7-fold compared with control) in human aortic smooth muscle cells specifically by activating membrane-associated NADPH oxidase, but not NADH or xanthine oxidase. This process was inhibited by an inhibitor of NADPH oxidase, diphenylene iodonium (DPI), and by antioxidants, N-acetyl-L-cysteine (NAC) or pyrrolidine dithiocarbamate. NAC and DPI both abrogated individual steps in the signaling pathway leading to cell proliferation. For example, the p21(ras).GTP loading, p44 MAPK activity, and induction of transcription factor c-fos all were inhibited by NAC and DPI as well as an antioxidant pyrrolidine dithiocarbamate or reduced glutathione (GSH). In contrast, depletion of GSH by L-buthionine (S, R)-sulfoximine up-regulated the above described signaling cascade. In sum, LacCer, by virtue of activating NADPH oxidase, produces superoxide (a redox stress signaling molecule), which mediates cell proliferation via activation of the kinase cascade. Our findings may explain the potential role of LacCer in the pathogenesis of atherosclerosis involving the proliferation of aortic smooth muscle cells.
...
PMID:Redox-regulated signaling by lactosylceramide in the proliferation of human aortic smooth muscle cells. 918 53

Muscle necrosis induced by various phenylenediamine derivatives has been correlated with their autoxidation rate. However, a more detailed investigation of the cytotoxic mechanism using a model system of isolated hepatocytes and 2,3,5,6-tetramethylphenylenediamine (DD) shows little oxygen activation as indicated by the absence of cyanide resistant respiration, lipid peroxidation and lack of cytoprotection by iron chelators, superoxide dismutase mimics and xanthine oxidase inhibitors. Cytotoxicity was however attributed to oxidative stress as GSH was not only rapidly oxidized to GSSG but mixed protein disulfide formation also occurred. Furthermore, the disulfide reductant dithiothreitol added some time after DD restored protein thiols and prevented further cytotoxicity. This oxidative stress was attributed to a futile two electron redox cycle involving oxidation of DD to the corresponding diimine by the mitochondrial electron transport chain and rereduction by DT diaphorase. Evidence suggesting this was that both diimine accumulation and the ensuing cytotoxicity were markedly increased by inactivating hepatocyte DT diaphorase but were prevented by a subtoxic concentration of the mitochondrial respiratory inhibitor cyanide. Furthermore, addition of NADH generating substrates such as lactate, sorbitol, xylitol or ethanol prevented DD induced GSH oxidation and cytotoxicity. This suggests that DD undergoes intracellular redox cycling without oxygen activation until the hepatocyte is unable to maintain redox homeostasis and mixed protein disulfide cytotoxicity ensues.
...
PMID:Phenylenediamine induced hepatocyte cytotoxicity redox. Cycling mediated oxidative stress without oxygen activation. 920 97

To clarify whether the changes of free radicals and its scavengers are induced by thyroid disorders, we measured levels of free radical scavengers and checked O2 radical generating systems in the human thyroid gland. Thyroid specimens from patients with Graves' disease, follicular adenoma, and papillary and follicular carcinomas contained significantly higher concentrations of xanthine oxidase (XOD) and gluthathione peroxidase (GSH-PX), compared to those in the normal thyroid tissue. Catalase concentration was significantly lower in thyroid specimens from patients with Graves' disease and significantly lower in thyroid specimens from patients with follicular adenoma, compared to those in the normal thyroid tissue. Cu/Zn superoxide dismutase (Cu/Zn SOD) concentration was significantly lower in the specimens from follicular adenoma and papillary carcinoma and Mn SOD concentration was significantly higher in the specimens from papillary carcinoma than those in the normal thyroid tissue. The lipid peroxide concentration, expressed as malondialdehyde (MDA) concentration, was significantly higher in the specimens from papillary carcinoma than those in the normal thyroid tissue. These findings suggest that the levels of free radicals are increased and are scavenged and catalyzed in the thyroid of Graves' disease, whereas free radicals and lipid peroxide are not completely scavenged in papillary carcinoma tissues, suggesting that these substances affect some role in cell function of thyroid tumors.
...
PMID:Changes in free radical scavengers and lipid peroxide in thyroid glands of various thyroid disorders. 928 68

In vitro oxyradical effects on SR Ca2+ regulation were studied by using a SR-containing cell-free preparation from scallop (Pecten jacobaeus) adductor muscle. Ca2+ variations were fluorimetrically detected after incubation with Fluo-3 in the presence of ATP. Exposure to Fe3+/ascorbate produced dose-dependent Ca2+ release from SR vesicles, eventually leading to massive Ca2+ loss. Exposure to hypoxanthine/xanthine oxidase also caused Ca2+ release but at a much slower rate. Pre-incubations with catalase or with the hydroxyl radical scavenger KMBA led to a significant decrease in the Fe3+/ascorbate-induced Ca2+ release rate and to a delay of massive Ca2+ loss. Pre-incubations with GSH or DTT strongly reduced the Ca2+ release caused by Fe3+/ascorbate and, moreover, they prevented massive Ca2+ loss from SR vesicles. Addition of GSH or DTT after Fe3+/ascorbate promptly reduced the Ca2+ release rate and delayed massive Ca2+ release. Pre-incubation with the SR Ca2+ channel blocker ruthenium red strongly reduced the Ca2+ release caused by Fe3+/ascorbate, and also prevented massive Ca2+ loss. In the presence of ruthenium red, Fe3+/ascorbate treatments followed by Ca2+ addition revealed that Ca2+ uptake inhibition was slower than Ca2+ release. Taken together, data showed that free radicals and, in particular, hydroxyl radicals, affected the scallop SR Ca2+ regulation. This mainly occurred through Ca2+ channel opening, most likely triggered by sulfhydryl oxidation, which eventually led to massive Ca2+ release from SR vesicles. The demonstration of a specific effect of oxyradicals on SR Ca2+ channels is in line with their possible involvement in cell signaling.
...
PMID:Effects of free oxygen radicals on Ca2+ release mechanisms in the sarcoplasmic reticulum of scallop (Pecten jacobaeus) adductor muscle. 929 26


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---