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 purposes of this study were to determine whether exercise training induces increases in skeletal muscle antioxidant enzymes and to further characterize the relationship between oxidative capacity and antioxidant enzyme levels in skeletal muscle. Male Sprague-Dawley rats were exercise trained (ET) on a treadmill 2 h/day at 32 m/min (8% incline) 5 days/wk or were cage confined (sedentary control, S) for 12 wk. In both S and ET rats, catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX) activities were directly correlated with the percentages of oxidative fibers in the six skeletal muscle samples studied. Muscles of ET rats had increased oxidative capacity and increased GPX activity compared with the same muscles of S rats. However, SOD activities were not different between ET and S rats, but CAT activities were lower in skeletal muscles of ET rats than in S rats. Exposure to 60 min of ischemia and 60 min of reperfusion (I/R) resulted in decreased GPX and increased CAT activities but had little or no effect on SOD activities in muscles from both S and ET rats. The I/R-induced increase in CAT activity was greater in muscles of ET than in muscles of S rats. Xanthine oxidase (XO), xanthine dehydrogenase (XD), and XO + XD activities after I/R were not related to muscle oxidative capacity and were similar in muscles of ET and S rats. It is concluded that although antioxidant enzyme activities are related to skeletal muscle oxidative capacity, the effects of exercise training on antioxidant enzymes in skeletal muscle cannot be predicted by measured changes in oxidative capacity.
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PMID:Skeletal muscle oxidative capacity, antioxidant enzymes, and exercise training. 238 14

Asbestos resembles the phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA), in its ability to elicit release of superoxide (O2-.) from rodent alveolar macrophages (AM) in vitro. In addition, superoxide dismutase (SOD), the antioxidant enzyme scavenging O2-, is increased in cultures of tracheobronchial epithelial cells and lung fibroblasts after exposure to either crocidolite or chrysotile asbestos. Our objectives here were to determine: (1) the chemical and physical properties of asbestos important in the generation of O2- from rat AM; and (2) the effects of O2- in comparison with asbestos on biosyntheses of collagen and non-collagen protein in rat lung fibroblasts in vitro. We were also interested in whether increased production of SOD occurred in the lungs of rats after inhalation of crocidolite asbestos. To determine whether O2- was elicited in response to a variety of asbestiform fibres, AM lavaged from Fischer 344 rat lungs were exposed in vitro to equivalent non-toxic amounts of crocidolite asbestos, erionite, Code 100 fibreglass, sepiolite, and their non-fibrous analogues, riebeckite, mordenite and glass particles. In addition, sized preparations of long (greater than 10 microns) and short (less than 2 microns) asbestos were introduced at identical concentrations to determine whether length of fibres is critical in O2- release. The amount of O2- released from AM in response to dusts was then determined by measuring SOD-inhibitable reduction of cytochrome C. All asbestiform fibres caused a significant (p less than 0.05) increase in generation of O2- from epithelial cells, whereas non-fibrous particles were less active at comparable concentrations. Experiments with long (greater than 10 microns) versus short (less than 2 microns) chrysotile showed that long fibres caused a more striking, dosage-dependent release of O2-. To determine whether O2- plays a role in the causation of fibrotic lung disease, rat lung fibroblasts were exposed to a biochemical generation system (xanthine-xanthine oxidase) for O2- before quantitation of cell-associated collagen and non-collagen protein at 24, 48 and 72 h thereafter. At the latter time periods, significant increases in total collagen per ng DNA were observed. In comparison with controls, the generation system for O2- also caused an initial decrease in synthesis of non-collagen protein followed by increases in synthesis of non-collagen protein at 48 and 72 h.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Mechanisms of fibre-induced superoxide release from alveolar macrophages and induction of superoxide dismutase in the lungs of rats inhaling crocidolite. 254 20

Evidence has been obtained that implicates the generation of reactive oxygen species as an early and critical event in the promotion of neoplastic transformation in mouse JB6 cells. The time courses for specific inhibition by CuZn-superoxide dismutase (CuZn-SOD) of the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced promotion of neoplastic transformation in JB6 cells and for changes in antioxidant enzyme activities associated with TPA-exposure were examined. The antipromoting effect of CuZn-SOD was found to be critically dependent on the time of addition of CuZn-SOD relative to the start of a 14-day exposure of cells to TPA. Treatment of JB6 P+ Clone 22 and Clone 41 cells with CuZn-SOD for 18 h before, simultaneously with or up to 1 h after exposure to TPA, all inhibited promotion of transformation maximally. Delay of addition of CuZn-SOD by 2 h or more after the start of TPA treatment resulted in a marked decrease in the promotion inhibitory effect. CuZn-SOD added 24 or 48 h after TPA had no effect on promotion of transformation. Exposure of JB6 cells to 0.2- (superoxide anion radical) generated exogenously by the aerobic xanthine oxidase reaction resulted in promotion of neoplastic transformation that was prevented by concurrent addition of CuZn-SOD. Taken together these studies provide evidence that increased superoxide anion generation within the first 2 h following TPA exposure is an essential event in promotion of transformation in JB6 cells. Upon TPA exposure, JB6 Clone 41 cells exhibited time-specific activity changes in the cellular SOD, glutathione peroxidase (GSH-Px), and catalase. SOD and GSH-Px activities were reduced to 54% and 26% respectively of basal levels within 2 h of TPA treatment. GSH-Px activity recovered to basal levels within 4 h and CuZn-SOD within 48 h. Catalase activity was maximally reduced to 50% of basal within 1 h after TPA treatment and rebounded to greater than basal levels within 4 h. It is postulated that a c-kinase-dependent event induces rapid elevation of superoxide anion following TPA exposure and that this leads to reduced activity of antioxidant enzymes. Since antipromotion by exogenous CuZn-SOD is effective only during the first 2 h following TPA exposure, this suggests that the promotion-relevant 0.2- elevation is transient.
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PMID:Early superoxide dismutase-sensitive event promotes neoplastic transformation in mouse epidermal JB6 cells. 282 3

Our previous in vivo study demonstrated that methylprednisolone (MP) activates glomerular antioxidant enzymes and attenuates glomerular oxidant injuries, including those in experimental nephrosis. The present study investigates the cellular mechanism of the MP-induced activation of antioxidant enzymes and their contribution to the attenuation of cellular oxidant toxicity. When bovine glomerular endothelial cells (GECs) were treated with 10 microM MP, cellular manganese superoxide dismutase (Mn-SOD, 3.95 +/- 0.33 mu/mg protein, M +/- SE) and catalase (1.64 +/- 0.06 k/mg protein) activities were significantly (P < 0.05) elevated above control GECs (2.23 +/- 0.43 mu/mg protein and 1.06 +/- 0.09 k/mg protein, respectively). When GECs pretreated with MP (10 microM 24 hrs) were exposed to xanthine (0.1 mM)+xanthine oxidase (5 mU/ml) for four hours, levels of specific membrane lipid peroxidation products, that is, phosphatidylcholine- and phosphatidylethanolamine-hydroperoxides, remained at levels 10 to 25% of those measured in non-MP-treated (xanthine/xanthine oxidase-exposed) control cells. Moreover, the degree of cell damage following exposure to the superoxide generating system, assessed by 51Cr release, was significantly attenuated in MP-treated cells (approximately 50% of MP-non-treated controls, N = 6). Thus, MP-treated GECs with elevated antioxidant enzyme activities by MP were more resistant to the toxic effect of reactive oxygen metabolites. The mechanism of antioxidant enzyme induction by MP was studied for Mn-SOD. MP was shown to enhance Mn-SOD mRNA in bovine GECs and rat glomerular mesangial cells (GMCs) in dose-dependent manners.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Induction of manganese superoxide dismutase by glucocorticoids in glomerular cells. 812 10

The effect of Adriamycin (ADM) administration on heart mitochondria was investigated in rats at rest and after an acute bout of maximal exercise. ADM was given intravenously at a dosage of 8 mg/kg body weight 24 and 1 hr before rats were decapitated. Respiratory functions of the isolated heart mitochondria were measured polarographically with both site 1 (pyruvate-malate and 2-oxoglutarate) and site 2 (succinate) substrates. State 4 (basal) respiration was increased using all substrates in ADM-treated rat hearts compared with non-drug control hearts. The mitochondrial respiratory control index was decreased with ADM, but the reduction was due to an increase in state 4 rather than a decrease of state 3 (ADP-stimulated) respiration. ADM administration abolished an exercise-induced elevation of state 3 respiration using all substrates. There was no significant myocardial oxidative damage of dysfunction as evaluated by lipid peroxidation and antioxidant enzyme activity. Addition of exogenous free radicals to the respiratory medium using hypoxanthine and xanthine oxidase resulted in significant deterioration of mitochondrial function in all parameters measured, but no drug- or exercise-specific patterns of damage were revealed. It is concluded that the current dose of ADM (20% of the established cumulative toxic dose) administered within 24 hr can interfere with normal heart mitochondrial function both at rest and during heavy exercise, but does not elicit overwhelming oxidative damage to the myocardium.
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PMID:Effects of Adriamycin on heart mitochondrial function in rested and exercised rats. 813 63

We quantitated the ability of intratracheally administered liposome-encapsulated antioxidant enzymes to reduce reactive oxygen species injury to the pulmonary microvasculature. Cationic liposomes containing 3,500 U of Cu,Zn superoxide dismutase (Cu,Zn SOD) and 3,124 U of catalase were instilled into rabbits. The animals were killed 2-72 h later and their lungs were removed and perfused with Krebs Ringer with 5% wt/vol of fat-free bovine serum albumin. The pulmonary filtration co-efficient (Kf,c) was measured before and after adding 500 microM xanthine and 5 mU/ml xanthine oxidase (XO) into the lung perfusate. Two hours after a single intratracheal instillation of liposome-entrapped Cu,Zn SOD and catalase, lung antioxidant enzyme activities were 34 and 125% higher than the corresponding control values, remained virtually unchanged for up to 8 h post-instillation, and then decreased, reaching baseline values between 24 and 72 h. Addition of xanthine and XO into the lung perfusate of un-instilled rabbits, or rabbits that received liposomes with inactivated enzymes, caused a 100% increase in Kf,c (control value: 2 +/- 0.12 ml.min-1 x cmH2O-1 per 100 g dry lung weight). On the other hand, Kf,c values of rabbits lungs instilled with liposome-encapsulated active Cu,Zn SOD and catalase and challenged with xanthine and XO 8-24 h later remained at baseline levels. Instillation of liposomes containing either enzyme was equally effective in preventing the increase in Kf,c, indicating that both superoxide anions and hydrogen peroxide were necessary for the initiation of injury. We concluded that intratracheal instillation of liposome-encapsulated antioxidant enzymes caused a transient increase of lung antioxidant enzyme levels which protects the pulmonary microvasculature from free radical-initiated injury.
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PMID:Mitigation of oxidant injury to lung microvasculature by intratracheal instillation of antioxidant enzymes. 823 68

In the present study, we investigated the effects of high levels of dietary fish oil on the growth of MX-1 human mammary carcinoma and its response to mitomycin C (MC) treatment in athymic mice. We found that high levels of dietary fish oil (20% menhaden oil + 5% corn oil, w/w) compared to a control diet (5% corn oil, w/w) not only lowered the tumor growth rate, but also increased the tumor response to MC treatment. We also found that high levels of dietary fish oil significantly increased the activities of tumor xanthine oxidase and DT-diaphorase, which are proposed to be involved in the bioreductive activation of MC. Since menhaden oil is highly unsaturated, its intake caused a significant increase in the degree of fatty acid unsaturation in tumor membrane phospholipids. This alteration in tumor membrane phospholipids made the tumor more susceptible to oxidative stress, as indicated by the increased levels of both endogenous lipid peroxidation and protein oxidation after feeding the host animals the menhaden oil diet. In addition, the tumor antioxidant enzyme activities, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPOx), and glutathione S-transferase peroxidase (GSTPx), were all significantly enhanced by feeding a diet high in fish oil. MC treatment caused further increases in tumor lipid peroxidation and protein oxidation, as well as in the activities of CAT, SOD, GPOx, and GSTPx, suggesting that MC causes oxidative stress in this tumor model which is exacerbated by feeding a diet high in menhaden oil. Thus, feeding a diet rich in menhaden oil decreased the growth of human mammary carcinoma MX-1, increased its responsiveness to MC, and increased its susceptibility to endogenous and MC-induced oxidative stress, and increased the tumor activities of two enzymes proposed to be involved in the bioactivation of MC, that is, DT-diaphorase and xanthine oxidase. These findings support a role of these two enzymes in the bioactivating of MC and indicate that the type of dietary fat may be important in tumor response to therapy.
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PMID:Dietary menhaden oil enhances mitomycin C antitumor activity toward human mammary carcinoma MX-1. 856 32

Generation of reactive oxygen species (ROS) is a common event in the pathogenesis of acute lung injury. Endothelial cells may be both a target and a source of the ROS. Exposure of bovine pulmonary endothelial cells (BPAEC) to lipopolysaccharide (LPS) has been shown to result in intracellular generation of both ROS and the antioxidant enzyme, mangano superoxide dismutase (MnSOD). The present study investigates whether alterations in intracellular oxidant state affect LPS-stimulated cytotoxicity and induction of MnSOD mRNA. BPAEC were pretreated with either the free radical scavenger, dimethylsulfoxide (DMSO), the xanthine oxidase inhibitor, allopurinol, or N-acetylcysteine (a cysteine derivate capable of increasing glutathione stores) prior to exposure to LPS (0.1 microgram/ml) for either 4, 8 or 18 hours. We found that pretreatment of BPAEC with DMSO blocked both LPS-induced cytotoxicity and induction of the MnSOD gene. Nuclear run-off experiments demonstrated that LPS-stimulated induction of the MnSOD mRNA occurred at the transcriptional level and that DMSO blocked this event. Pretreatment with allopurinol also prevented the cytotoxicity associated with LPS but, in contrast to DMSO, did not alter induction of MnSOD mRNA. N-acetylcysteine did not affect the LPS-stimulated cytotoxicity but resulted in an early and transient reduction in induction of the MnSOD gene. We conclude that LPS stimulates generation of intracellular ROS that regulate induction of the MnSOD gene at the transcriptional level further, we conclude that LPS-stimulated cytotoxicity involves both the xanthine oxidase pathway and perhaps intracellular generation of hydroxyl radicals. The difference in the protective effect between DMSO, NAC and allopurinol suggest that upregulation of the MnSOD gene does not contribute to LPS-induced cytotoxicity.
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PMID:Effect of antioxidants on lipopolysaccharide-stimulated induction of mangano superoxide dismutase mRNA in bovine pulmonary artery endothelial cells. 890

We investigated the effects of aging and/or swimming training on the antioxidant enzyme system in diaphragm of mice. Young (2 months old) and old (26 months old) male mice were swimming-trained for 6 weeks (1 h/day, 5 days/week). Cu,Zn-Superoxide dismutase (Cu,Zn-SOD) activity was significantly upregulated with aging, and swimming training definitely enhanced the activity only in young mice. Neither aging nor swimming training had overt effect on Mn-SOD activity. Glutathione peroxidase activity in young mice was significantly increased after training, but not in old mice. Both of immunoreactive Cu,Zn-SOD and Mn-SOD were significantly increased with aging but were unaffected by swimming training. Consequently, physical training significantly enhanced the specific activity of Cu,Zn-SOD in young mice, but not in old mice. Meanwhile, swimming training significantly increased xanthine oxidase activity in both age groups, the extent of the increase being greater in old mice than in young mice. We concluded that the antioxidant enzyme system in mouse diaphragm trends to be upregulated with aging, but that swimming training improved the system only in young mouse diaphragm.
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PMID:Effects of aging and/or training on antioxidant enzyme system in diaphragm of mice. 893 Nov 79

Nitric oxide mediates esophageal peristalsis and lower esophageal sphincter (LES) relaxation. Superoxide produced with inflammation inactivates nitric oxide. Superoxide is cleared in biological systems by superoxide dismutase. We tested the hypothesis that superoxide and the superoxide scavenging system modulate LES function. Transverse strips of muscle from the opossum LES relaxed when stimulated by an electrical field. Diethyldithiocarbamite was used to inhibit copper/zinc superoxide dismutase. Xanthine and xanthine oxidase were used to generate superoxide. Xanthine with xanthine oxidase or diethyldithiocarbamite alone had no effect on the LES. However, xanthine/xanthine oxidase and diethyldithiocarbamite reduced LES relaxation 34.1% and increased its resting tone 71.2%. Superoxide dismutase did not affect LES function, but protected the tissue from the effects of diethyldithiocarbamite and xanthine/xanthine oxidase. These studies are consistent with the hypothesis that superoxide acts by inactivating nitric oxide and suggest that these antioxidant enzyme systems may play a role in the maintenance of LES function.
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PMID:Effects of oxygen radicals and radical scavenging on opossum lower esophageal sphincter. 907 44


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