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

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Query: EC:1.16.3.1 (ceruloplasmin)
5,074 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Copper is an essential metal during development. Female Swiss Webster mice were fed a modified AIN-76A diet low in copper (0.3 mg Cu/kg and 43 mg Fe/kg; -Cu). One-half the mice received copper in their drinking water (20 mg Cu/L; +Cu). Female mice were mated to normal males and offered the -Cu or +Cu treatments starting at gestational d 13. Treatments did not affect litter size or pregnancy outcome. For three litters of +Cu mice, 26/26 offspring born were weaned on postnatal d 21 (P21). For three litters of -Cu dams, 0/26 pups survived beyond P13. The -Cu dams kept on treatment for this 3-wk period were killed and compared biochemically with +Cu dams and to nonpregnant females that were kept on the +Cu or -Cu treatment and fed the same diet for 3 wk. Compared with +Cu dams, -Cu dams had 48% lower hematocrits, 89% lower plasma ceruloplasmin activities, 45% lower liver copper level, and > 2-fold higher liver iron concentration. The -Cu, nonpregnant female mice did not differ in any of these copper status indicators from the +Cu dams or nonpregnant, +Cu females. When -Cu treatment was delayed until embryonic d 19, all -Cu pups survived weaning. Additional studies should be conducted to establish the human copper requirement for perinatal development and determine whether the 11 and 44% extra copper intakes recommended for pregnancy and lactation in the new United States recommended dietary allowance are sufficient.
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PMID:The timing of perinatal copper deficiency in mice influences offspring survival. 1236 85

It is thought that changes in gene expression in the brain mediate chronic ethanol-induced complex behaviors such as tolerance, dependence, and sensitization, and also relate to ethanol-induced brain toxicity. Using high-density filter-based cDNA microarrays (GeneFilters), we analyzed the expression of over 5000 genes in the dorsal hippocampus of rats treated with 12% ethanol or tap water for 15 months. Ethanol-induced changes in gene expression were particularly prominent in two groups of genes. One group consisted of oxidoreductases, including ceruloplasmin, uricase, branched-chain alpha-keto acid dehydrogenase, NADH ubiquinone oxidoreductase, P450, NAD+-isocitrate dehydrogenase, and cytochrome c oxidase, which may be related to ethanol-induced oxidative stress. The other group of genes included ADP-ribosylation factor, RAS related protein rab10, phosphatidylinositol 4-kinase, dynein-associated polypeptides, and dynamin-1, which seem to be involved in membrane trafficking. The results may reveal some of the pathways involved in ethanol-induced pathophysiological changes.
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PMID:Microarray analysis of gene expression in rat hippocampus after chronic ethanol treatment. 1246 20

Copper in drinking water has been associated with Non-Indian Childhood Cirrhosis (NICC), a form of early childhood liver cirrhosis. This epidemiological study examines the exposition of infants to increased copper concentrations through drinking water from public water supplies in Berlin, Germany, and if this dietary copper intake can cause liver damage in early childhood. In total, water samples from 2944 households with infants were tested for copper. Mean copper concentrations in the two different types of collected composite samples were 0.44 and 0.56 mg/l, respectively. Families having a copper concentration at or above 0.8 mg/l in one or both of the composite samples (29.9% of all sampled households) and a defined minimum ingestion of tap water of their infant were recommended to undergo a paediatric examination. Nearly every of the 541 recommended infants were examined by a local paediatrician and of these 183 received a blood serum analysis, too. None of the infants had clear signs of a liver disease although a few serum parameters lay outside the accompanying reference range and abdominal ultrasound imaging gave slightly unusual results in five cases. Additionally, no signs of a negative health effect could be found in the statistical analysis of the serum parameters GOT, GPT, GGT, total bilirubin, serum copper, or ceruloplasmin in relation to estimated daily and total copper intakes of the infants from tap water. No dose relation of serum parameters and estimated copper intakes could be established. From the results of the study, no confirmed indication of a liver malfunction in infants whose food had been prepared using tap water with an elevated copper concentration could be found and, therefore, no indication of a hazard due to copper pipes connected to public water supplies could be detected.
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PMID:Epidemiological investigation on chronic copper toxicity to children exposed via the public drinking water supply. 1252 4

The present paper describes a protective role of L-tyrosine against aggregation of caeruloplasmin and haemoglobin therapeutic proteins during their sterilization by gamma-irradiation in the aqueous phase. Irradiation of proteins, known to induce their degradation in the presence of oxygen, generates aggregation under oxygen-free conditions. It was found that L-tyrosine present during irradiation in deoxygenated media prevents protein aggregation even at high doses (10 kGy), as asserted by SDS/PAGE and high-performance size-exclusion chromatography. The protective role of L-tyrosine, allowing the gamma-irradiation treatment of therapeutic proteins in solution without conformational alteration, is probably exerted by scavenging oxygen radicals produced by irradiation-induced water radiolysis. It was also found that haemoglobin had a greater stability than caeruloplasmin under gamma-irradiation treatment.
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PMID:L-tyrosine prevents aggregation of therapeutic proteins by gamma-irradiation. 1277 96

Aegle marmelos Corr. (Rutaceae) is widely used in Indian Ayurvedic medicine for the treatment of diabetes mellitus. The hypoglycaemic effect of the water extract of the fruits of Aegle marmelos was examined in streptozotocin-induced diabetic Wistar rats. Oral administration of the water extract (125 and 250mgkg(-1)) twice a day for 4 weeks resulted in significant reductions in blood glucose, plasma thiobarbituric acid reactive substances, hydroperoxides, ceruloplasmin and alpha-tocopherol and a significant elevation in plasma reduced glutathione and Vitamin C in diabetic rats. The effect of the extract at a dose of 250mgkg(-1) was more effective than glibenclamide in restoring the values of these parameters. The results of this study clearly shows the hypoglycaemic activity of the fruit extract.
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PMID:Hypoglycaemic effect of water extracts of Aegle marmelos fruits in streptozotocin diabetic rats. 1286 Mar 9

Body iron status regulates ferroportin-1 (FPN1) expression such that intestinal mRNA levels are enhanced by anemia, whereas liver transcripts are increased by iron overload. In vitro evidence suggests that copper also upregulates FPN1. To investigate whether copper deficiency affects FPN1 expression in vivo, starting at gestation d 17, pregnant mice were fed a modified AIN-76A diet low in copper (-Cu). Half of the mice were given copper in drinking water (+Cu). At 28 d, -Cu pups had significantly lower copper concentrations in duodenum, liver, and kidney (63, 50, and 27%, P < 0.01) and >95% loss of ceruloplasmin activity. -Cu mice also had reduced hemoglobin (81.8 vs. 124.4 g/L in +Cu mice) and hematocrits (0.35 vs. 0.46 in +Cu mice), and displayed hepatic iron-loading (2- to 3-fold relative to +Cu mice). Despite these changes in copper and iron status, FPN1 mRNA levels were not altered significantly in duodenum, liver, kidney, and spleen. Moreover, FPN1 protein levels were not altered in liver tissue from -Cu mice, despite hepatic iron-loading. These data indicate that tissue copper deficiency does not alter FPN1 expression but that copper adequacy may be required for appropriate regulation of FPN1 by iron status.
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PMID:Ferroportin-1 is not upregulated in copper-deficient mice. 1498 40

As an environmental protection point of view, the potential toxicity of chitosan on aquatic animal health, alone or associated with copper must be investigated. Fish possess defence mechanisms to counteract the impact of toxics. The non-cellular and non-specific immune defences (total immunoglobulin, ceruloplasmin, lysozyme and potential killing activity of phagocytic cells) can be modulated by the potential environmental pollutants but also by natural stimulants such as bacteria, viruses or parasites. In this study, we investigate the potential toxicity of copper (0.1 and 0.25 mg/L) or chitosan (75 and 150 mg/L) and the combination copper and chitosan (0.1 and 75 mg/L, respectively) on two groups of carp: healthy or parasitised by Ptychobothrium sp. Fish exposed to water-soluble chitosan for 96 h had significantly high levels of natural antibodies in plasma. Moreover, activities of lysozyme and ceruloplasmin were also increased in plasma after the same treatment. The exposition of fish to copper have shown apparently contradictory effects on the immune parameters measured but, significant increase of this bacteriolytic activity was observed, particularly in head kidney after 4 days of treatment of fish with copper. The two products may induce separately an acute, short and local inflammatory acute phase response by stimulating some components of the innate immune response of healthy fish. The mixture seems to reduce the impact of the each product due to the physical and chemical properties of chitosan to complex with copper. The responses of humoral immune factors of treated carp was modulated by the presence of the parasite, as shown by the high elevation of lysozyme activity observed in parasitised carps after exposition to copper and by increases in natural antibodies levels observed in parasitised carp treated with the copper-chitosan mixture. This could indicate an additive effect on the stress response mediated by parasite. It occurred a greater stress response in the parasitised group than healthy group exposed to the same treatment evoking an additive effect. So, it is important to specify the health status of organisms to understand responses of immunological markers in fish.
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PMID:Humoral immune factors modulated by copper and chitosan in healthy or parasitised carp (Cyprinus carpio L.) by Ptychobothrium sp. (Cestoda). 1517 50

It has previously been shown that dietary copper can modulate the extent of atherosclerosis in the thoracic aorta of cholesterol-fed rabbits. The metabolism of copper and zinc are closely related, and it has been hypothesized that the balance of dietary copper to zinc may be important in determining coronary risk. Hence, we have investigated the interaction between dietary copper and zinc in atherogenesis in the New Zealand White rabbit. Juvenile male rabbits were randomly allocated to eight groups. Four groups were fed a normal chow diet with zinc (0.5%, w/w), copper (0.2%, w/w), copper plus zinc or neither in their drinking water for 12 weeks. Four other groups were fed a diet containing 0.25-1% (w/w) cholesterol plus zinc, copper, both or neither. Serum cholesterol of individual animals was maintained at approximately 20 mmol/l. Integrated plasma cholesterol levels were similar for all groups receiving cholesterol and significantly higher than those in the chow-fed groups (P < 0.001). Aortic copper concentrations were higher in the animals receiving cholesterol diets with copper compared to rabbits receiving normal chow and copper (P < 0.001). Aortic zinc content was significantly higher in cholesterol-fed rabbits supplemented with zinc alone or with copper than in those fed cholesterol alone (P < 0.001). Plasma ceruloplasmin concentrations were significantly higher in groups receiving cholesterol, irrespective of their trace element supplementation (P < 0.001). However, trace element supplementation increased the level significantly (P < 0.05). Trace element supplements did not appear to affect erythrocyte superoxide dismutase in the cholesterol-fed animals; however, zinc supplementation was associated with a significant increase in the enzyme in chow-fed animals (P < 0.05). The activity of the enzyme per mg of protein in aortic tissue was higher in animals receiving copper in the presence of cholesterol (P < 0.05) but not significantly so in its absence. Dietary trace element supplementation in cholesterol-fed animals was associated with a significant reduction in aortic lesion area. Plasma thiobarbituric acid-reactive substances and FOX concentrations were both significantly higher in the cholesterol-fed rabbits compared with the animals that fed on a chow diet (P < 0.001), and these were reduced significantly by dietary copper or zinc supplementation (P < 0.001). Hence, dietary supplements of copper or zinc at the doses used both inhibited aortic atherogenesis in the cholesterol-fed rabbits, although there was no significant additional effect when given in combination.
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PMID:The effects of coadministration of dietary copper and zinc supplements on atherosclerosis, antioxidant enzymes and indices of lipid peroxidation in the cholesterol-fed rabbit. 1537 59

The stable isotope tracer approach was explored for long-term investigations of copper turnover in the adult rat and mouse, with inductively coupled plasma mass spectrometry for isotope measurements. The isotopic measurement method permitted precision and accuracy of <1.0%, with an overall sample blank of <0.05 microg copper. Rats were fed a copper-deficient diet and deionized water with (+Cu) or without (-Cu) copper (20 microg/ml). Both groups underwent a single-day replacement of drinking water with 20 microg/ml of (65)Cu. Compared with the baseline isotope ratio ((65)Cu/(63)Cu) of 0.462 +/- 0.002, blood plasma ratios for the +Cu group on days 2, 7, and 14 postdosing were 0.702 +/- 0.021, 0.557 +/- 0.004, and 0.474 +/- 0.001, respectively. The corresponding data for liver were 1.652 +/- 0.018, 0.560 +/- 0.005, and 0.482 +/- 0.001, respectively. For the -Cu group, respective plasma ratios were 1.580 +/- 0.04. 0.917 +/- 0.02, and 0.664 +/- 0.01 for days 2, 7, and 14 postdosing, and the ratios for liver were 0.987 +/- 0.02, 0.876 +/- 0.04, and 0.739 +/- 0.03. Mice previously made copper deficient to varying degrees were given a single-day replacement with the label. When the 24-hour postdosing isotope ratios in the livers of these mice were correlated with the activity of plasma ceruloplasmin, a negative correlation (r = -0.85) was observed. Isotope enrichment in both rats and mice was greater in the copper-deficient animals compared with the controls.
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PMID:Development of the stable isotope tracer approach for studies of copper turnover in the rat and mouse. 1553 12

Dietary copper (Cu) deficiency was produced in Swiss albino mice to determine the temporal relationship between depletion of Cu and changes in the cardiovascular and nervous system. Dams were placed on a Cu-deficient diet 4 days after parturition. Half the dams were provided with deionized water and their offspring are referred to as Cu-deficient (-Cu). Half the dams were given cupric sulfate in their drinking water (20 microg Cu/mL) and their offspring are referred to as Cu-adequate (+Cu). At 6 weeks of age a sample of the -Cu mice were repleted with CuSO(4). Mice were sampled 1 day after birth and at weekly intervals for 7 weeks. Both +Cu and -Cu mice grew at the same rate: birth weight increased 16-fold at 6 weeks of age. Liver Cu more than doubled between 1 and 7 days of age. At 2 weeks of age -Cu mice were anemic (lower hematocrit and hemoglobin) and had lower liver Cu and plasma ceruloplasmin activity compared to +Cu mice. Liver Fe was not elevated in -Cu mice until 2 weeks after anemia developed. At weaning first signs of altered catecholamine metabolism included elevation of dopamine in both heart and spleen. Norepinephrine concentrations and content, in contrast, were not both lowered in -Cu mice until 5 weeks of age. Heart weight was first elevated in -Cu mice at 6 weeks of age and relative weight (mg/g body wt) at 4 weeks of age. Liver Cu concentration was lower in 1-week repleted mice than in +Cu mice. Anemia preceded the development of cardiac hypertrophy and altered catecholamine levels in -Cu mice.
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PMID:Development of copper deficiency in neonatal mice. 1553 31


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