Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.16.3.1 (ceruloplasmin)
5,074 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Superoxide (.O-2) is demonstrated to participate at the prostaglandin phase swelling (2-4 h) of carrageenan paw edema. Superoxide production is inhibited in vitro by typical anti-inflammatory drugs, but these drugs did not scavenge superoxide which was produced by xanthine oxidase. Phosphate, pyrophosphate, ATP, ADP and sulfate were essential for superoxide production by macrophages. These anions can induce paw swelling and are reported to increase in rheumatic patients. A mixture of macrophages and lymphocytes from BCG sensitized guinea-pigs was cultured for 2 days with SOD or D-mannitol. Nitroblue tetrazolium reduction (formazan formation) was inhibited by these agents, suggesting that the hydroxyl radical (.OH) is necessary for metabolic activation of macrophage. Lympholine-like factor of which production or release is enhanced by hydroxyl radical, activates macrophage. Production of oxygen radicals may increase rapidly by this chain cycle reaction. Possible relations of oxygen radicals to prostaglandin(s) biosyntheses, chemotaxis, lysosomal enzyme release protease participation, were discussed. Endogenous SOD, epinephrine, ceruloplasmin, blood plasma proteins, inflammatory fluid, may modulate the amount of superoxide by their superoxide scavenging capacities.
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PMID:Inflammation and superoxide production by macrophages. 626 69

Superoxide anion radicals have been implicated recently as mediators of inflammation and tissue injury. Protection from superoxide anion radicals is provided primarily by a copper-containing, intracellular enzyme (superoxide dismutase) (SOD) that catalyzes the dismutation of superoxide to hydrogen peroxide and oxygen. We have found that the action of cytoplasmic SOD to scavenge superoxide and thereby to inhibit superoxide-mediated reactions can be mimicked by the copper-containing plasma protein and acute-phase reactant, ceruloplasmin. Ceruloplasmin, at concentrations present in normal plasma, inhibited reduction of both cytochrome c and nitroblue tetrazolium (NBT) mediated by the aerobic action of xanthine oxidase on hypoxanthine (a superoxide-generating system). Ceruloplasmin neither inhibited formation of uric acid by xanthine oxidase nor accelerated autooxidation of cytochrome c. Furthermore, in an experimental system in which contact between ceruloplasmin and indicator was prevented by a relatively impermeable lipid membrane barrier, ceruloplasmin inhibited reduction of NBT trapped within liposomes exposed to xanthine oxidase and hypoxanthine. Ceruloplasmin also inhibited reduction of cytochrome c and NBT mediated by the aerobic action of xanthine oxidase on acetaldehyde (another superoxide-generating system) and mimicked the activity of purified human erythrocyte SOD by inhibiting photoreduction of NBT and by accelerating aerobic photooxidation of dianisidine. Ceruloplasmin could be separated from purified human erythrocyte SOD by electrophoresis on alkaline 12% polyacrylamide gels and identified by its superoxide-scavenging activity. These results suggest that ceruloplasmin may function as a circulating scavenger of oxygen-derived free radicals.
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PMID:Ceruloplasmin: an acute phase reactant that scavenges oxygen-derived free radicals. 628 6

Using the spin-trapping technique, irradiation with visible light of complexes between DNA and proflavine was shown to generate OH radicals. The characteristic spectra were not obtained when proflavine or DNA were irradiated alone, nor when oxygen was absent. Using DMPO as a spin trap we found that the intensity of the DMPO-OH e.p.r. signal was enhanced when the molar ratio between bound proflavine and the DNA phosphorus increased up to a value of 0.15 demonstrating the efficiency of the intercalated dye molecules. A strong decrease of the e.p.r. signal was observed in the presence of various OH. scavengers like t-butanol, isopropanol or sodium benzoate. The OH. production was also decreased when the irradiation was made in the presence of SOD, ceruloplasmin or catalase and after addition of Chelex 100 resin.
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PMID:Visible-light-induced OH radicals in DNA-proflavine complexes: an e.p.r. and spin trapping study. 629 Apr 10

The effects of feeding rats high levels of dietary zinc (240 mg Zn/kg diet) on the activities of the copper-requiring metalloenzymes: ceruloplasmin (Cp), cupro -zinc superoxide dismutase (SOD) and cytochrome c oxidase (CCO) were determined. These were compared with those seen during copper deficiency (induced by feeding 0.6 mg Cu/kg diet). The activities of Cp in serum, Cu-Zn SOD in liver and heart, and CCO in heart were significantly reduced in both the high zinc and copper-deficient groups by 2 weeks, when compared to the activities seen in rats fed the control diet (6 mg Cu, 30 mg Zn/kg diet). In animals fed the high zinc diet, the reduction in heart CCO activity followed the decrease seen in heart copper concentration, whereas in blood and liver, the reductions in Cp and SOD activities, respectively, were greater than the reductions seen in copper concentration. Thus, the results of this experiment demonstrate that with high dietary zinc, the reductions seen in the activity of copper-requiring metalloenzymes were similar to those seen during copper deficiency.
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PMID:The effects of high dietary zinc and copper deficiency on the activity of copper-requiring metalloenzymes in the growing rat. 632 57

It has been known that there is remarkable antioxidant activity in the human sera, especially those in inflammation and pregnancy. In the present investigation, various sera were examined for the antioxidant activity with the aid of cultured cells. It was recognized that the serum added to the culture medium protected cells from harmful action of active oxygen generated by a hypoxanthine-xanthine oxidase (HX-XO) system. The inflammatory serum has the greatest protective power, followed by pregnant and normal sera in this order. The antioxidant activity of the serum was inversely related to the Fe concentrations. The addition of ceruloplasmin with SOD action could not inhibit the tissue damage, while addition of catalase or hemoglobin with catalase activity could inhibit it. The protective effect was valid against not only HX-XO, but also H2O2. These results show that the chief active oxygen to cause cell damage is H2O2 and the scavenger antioxidants in the serum are hemoglobin and catalase.
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PMID:Protective effect of the serum against cellular damage by active oxygen in culture. 654 44

Values for ceruloplasmin activities and copper concentrations were found to be lower in serum than in paired samples of plasma in both sheep and cattle. Ceruloplasmin activities in serum were 13-40% lower relative to plasma for nine different groups of animals, and 10-65% lower for individual animals (n = 112). As the values are not directly interchangeable, plasma rather than serum should be used when estimating copper nutrition in these animals. Maximum effects in serum were apparent 3-4 h after collection, the earliest time at which serum could be obtained. Lower ceruloplasmin and copper values in serum could not be attributed to the type of blood collection vessel used, subsequent storage of samples, the methods used for measuring ceruloplasmin activities and copper concentrations, the formation of fibrin in blood, or to the effects of dietary molybdenum. In contrast, the addition of neuraminidase to whole blood before clotting decreased the differences between serum and plasma ceruloplasmin activity and copper concentration in a dose-dependent manner. Of the two major copper-containing enzymes present in blood, effects of clotting were only evident with ceruloplasmin. Cu-Zn-containing superoxide dismutase activity in erythrocytes was unaffected by clot formation. The results indicate that ceruloplasmin and the copper associated with this protein are sequestered into the clot during clot formation by attachment of the enzyme to the blood cellular fraction. The minimizing of this effect by the addition of neuraminidase suggests that this attachment may be through sialic acid residues.
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PMID:Differences between serum and plasma ceruloplasmin activities and copper concentrations: investigation of possible contributing factors. 715 92

In a patient with typical copper deficiency, we found superoxide dismutase (SOD, 1.15.1.1) activity and copper in erythrocytes to be decreased to 52% and 46% of age-matched controls, respectively. However, these were not so markedly depleted as plasma copper (17%) or ceruloplasmin (20%). After copper replacement therapy, erythrocyte copper and SOD activity gradually returned to the control levels. Although certain abnormalities reported in copper deficiency in animals were expected, osmotic fragility of the liver and heart were not a feature as far as could be determined by electrocardiography and routine laboratory examinations. Probably a decrease of SOD to this extent is not severe enough to lead to superoxide-induced damage.
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PMID:Changes in erythrocyte superoxide dismutase in a patient with copper deficiency. 743 97

The aim of the paper was to compare the erythrocyte serum and hepatic chomogenate antioxidative factors in order to assess their involvement in the detoxification events. The catalase and superoxiddismutase levels, important factors of the cellular defence, were sensitivity modulated in an acute experiment on Wistar rats. Carbofuran was administered in a non-lethal dose (7 mg/b.w.) single or in the presence of certain antioxidative agents (Vitamin E, Caffeine, Aspirin) EDTA and Cysteine for their role in protecting membranes against oxidative damage. The erythrocyte parameters (SOD, Catalase) were well related to seric factors, especially ceruloplasmin level, with varied magnitudes. GGT a marker of hepatotoxicity and G1-DH, a mitochondrial marker, were in a good correlation with erythrocyte factors. The changes seem to modulate a transmembranary disturbance process, as in hepatocyte pictures.
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PMID:Interference of some enzymatic modulators in the hepatic aggression induced by xenobiotics. 754 89

We are constantly exposed, throughout life, to a wide variety of extrinsic and intrinsic agents which have the potential to damage cellular biomolecules, including DNA. Imperfections in cellular defence systems which protect against the fixation of DNA damage can lead to an accumulation of mutations which on their own, or in combination with other age-related changes, may contribute to ageing and the development of age-related pathologies. We have previously reported an increase in frequency of mutation with age in human lymphocytes taken from healthy males in the age groups, 35-39, 50-54 and 65-69 years. In this article we report on the findings of a recent study which was designed to assess whether the age-related increase in frequency of mutation was due to a decreased efficacy of the defence systems against ROS-induced DNA damage, namely antioxidant status and DNA repair processes, in the same study subjects. In vivo antioxidant status was assessed in each of the study subjects by measuring blood levels of; superoxide dismutase (SOD; EC 1.15.1.1), glutathione peroxidase (GPx; EC 1.11.1.9), catalase (EC 1.11.1.6), caeruloplasmin (CPL), uric acid and bilirubin. We did not find any statistically significant differences in the mean levels of these antioxidants between the three different age groups. To investigate the efficacy of DNA repair processes against ROS-induced DNA damage, an ELISA was used to quantitate DNA damage (as % single-stranded DNA; %SS-DNA) at various times following treatment of peripheral blood lymphocytes with hydrogen peroxide (H2O2). The results of this part of the study showed that in untreated lymphocytes, basal levels of %SS-DNA were significantly higher in individuals from the 65-69 years age group compared to the 35-39 years age group (p = 0.039, 0.0013; at 5% level of significance). No significant differences were found in H2O2 susceptibility with age immediately following treatment (p = 0.71, 1.00; at 5% level of significance) but a consistent and significant increase was observed in %SS-DNA remaining 90 min post-treatment in lymphocytes from subjects in the 65-69 years age group, compared to %SS-DNA present in lymphocytes from the 35-39 years age group (p = 0.013, 0.024; at 5% level of significance). The results of this study suggest that the age-related increase in frequency of mutations is not contributed to by alterations of in vivo antioxidant status with age but is by a decreased efficacy of the repair of ROS-induced DNA damage with age. The biological implications of somatic mutations in the ageing process are discussed.
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PMID:An investigation of antioxidant status, DNA repair capacity and mutation as a function of age in humans. 756 67

Six- and 24-month-old rats were fed a copper deficient diet for 10 weeks; the copper content of the diet was one fourteenth that of a control diet. After the 10-week feeding period, the copper contents of the cerebrums, livers, lungs, and serum were decreased by 20-17, 49-47, 48-37, and 84-83%, respectively, while those of hearts and muscles were unchanged or only slightly decreased. There was no difference in the decreases in copper content of tissues between young and old rats. Copper deficiency decreased the activity level of ceruloplasmin in the serum of young and old rats by 95%, and the copper/zinc superoxide dismutase (CuZn-SOD) activity levels of cerebrums, lungs, and livers of young rats by 16, 36, and 34%, respectively, but did not change the CuZn-SOD activity levels of tissues of old rats. Although copper deficiency affected catalase activity, vitamin E concentration, and reduced glutathione concentration in several tissues, no consistent trends were observed. On the basis of the survival time of rats exposed to more than 96% oxygen, it is suggested that a decrease in CuZn-SOD activity due to copper deficiency increases oxygen susceptibility.
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PMID:Effect of copper deficiency on the activity levels of ceruloplasmin and superoxide dismutase in tissues of young and old rats. 759 50


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