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)

We studied the effect of the plant alkaloid castanospermine on the biosynthesis and secretion of human hepatoma glycoproteins. The HepG-2 cells, grown in the presence or absence of the alkaloid, were labelled with [2-3H]mannose and then the labelled glycopeptides were prepared by Pronase digestion. This material was analysed by gel filtration on Bio-Gel P-4 before and after treatment with endo-beta-N-acetylglucosaminidase H. Castanospermine caused an accumulation of high-mannose oligosaccharides, by 70-75% over control. The major accumulated product, which could also be labelled with [3H]galactose and was only partially susceptible to alpha-mannosidase digestion, was identified by h.p.l.c. as a Glc3Man9GlcNAc. Thus the alkaloid inhibits glucosidase I in the human hepatoma cells. Analysis of total glycoproteins secreted by the cells into the medium revealed the presence of only complex oligosaccharides in both control and treated cultures, and the amount of the oligosaccharides labelled with radioactive mannose, galactose or N-acetylmannosamine, secreted by treated cells, was decreased by about 60%. The rate of secretion of total protein labelled with [35S]methionine and precipitated from the medium with trichloroacetic acid was inhibited by up to 40% in the presence of castanospermine. Pulse-chase studies utilizing [35S]methionine labelling were performed to study the effect of the alkaloid on secretion of individual plasma proteins. Immunoprecipitation at different chase times with monospecific antisera showed that castanospermine markedly decreased the secretion rates of alpha 1-antitrypsin, caeruloplasmin and, to a lesser extent, that of antithrombin-III. Secretions of apolipoprotein E, a glycoprotein containing only O-linked oligosaccharide(s), and albumin, a non-glycosylated protein, were not affected by the drug. It is suggested that castanospermine inhibits secretion of at least some glycoproteins containing N-linked oligosaccharides, owing to the inhibition of oligosaccharide processing.
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PMID:Castanospermine inhibits glucosidase I and glycoprotein secretion in human hepatoma cells. 300 19

Three patients with Menkes' disease, an inherited disorder of copper transport, were studied to determine whether the copper deficiency was associated with a lipoprotein disorder. Hypocuprinemia was documented in all three cases. Two patients had severe copper and ceruloplasmin deficiencies, whereas the third patient had a less severe deficiency. Hypertriglyceridemia was observed in the first patient, and elevations in triglyceride, cholesterol, apolipoprotein B (ApoB), and apolipoprotein C-III (ApoC-III) occurred predominantly in the very low density lipoprotein fraction (VLDL). This patient had normal lipoprotein lipase activity but mild glucose intolerance. The second patient had a borderline high cholesterol level with normal plasma triglycerides and apolipoproteins, whereas the third patient appeared to have normal total cholesterol but slightly higher triglycerides with elevated plasma apolipoprotein E (ApoE). No striking differences were observed in the chemical composition of all lipoprotein subfractions between patients and controls except that the neutral lipid content of VLDL was higher in patients than in controls. The ApoB was initially normal in molecular weight but degraded faster than the controls during storage. The appearance of the major low density lipoprotein (LDL) fraction of the first two patients was opaque white, in contrast to clear yellow in the third patient and in the age- and diet-matched controls. This abnormal appearance of LDL in these patients was associated with low plasma levels of beta-carotene and ceruloplasmin. These findings suggest that decreased serum copper levels may be associated with lipid and lipoprotein abnormalities and may enhance lipid peroxidation of LDL accounting for the color change.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Studies of lipids, lipoproteins, and apolipoproteins in Menkes' disease. 648 10

To examine the relationship between apolipoprotein E and serum oxidation status, we assayed apolipoprotein E level, apolipoprotein E phenotype, and levels of lipid peroxides and transition metal ions and their binding proteins in sera from apparently healthy individuals. The study group included 129 women aged 22-63 years and 53 men aged 22-56 years. Among subjects with apolipoprotein E 4/3 phenotype, lipid peroxide levels were higher compared with E 3/2 phenotype (786 +/- 182 nmol/l vs. 659 +/- 174 nmol/l, P = 0.015), and ceruloplasmin levels were slightly higher compared with apolipoprotein E 3/3 phenotype (0.28 +/- 0.08 mg/l vs. 0.26 +/- 0.06 mg/l, P = 0.035). In the study group as a whole, there were significant associations between serum apolipoprotein E level, and serum levels of ceruloplasmin (r = 0.266, P < 0.001) and ferritin (r = 0.2, P < 0.007). Among subjects with apolipoprotein E 4/3 phenotype, there was a significant association between serum apolipoprotein E and lipid peroxide levels (r = 0.470, P < 0.01), which was not apparent among subjects with E 3/3 or E 3/2 phenotypes. In multivariate analysis, apolipoprotein E phenotype was a small but significant independent contributor to variation in serum lipid peroxide levels. These data suggest that there may be heterogeneity among apolipoprotein E phenotypes in their relationships with serum lipid oxidation status.
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PMID:The relationship between apolipoprotein E and serum oxidation-related variables is apolipoprotein E phenotype dependent. 968 54

A better understanding of the molecular circuitry in normal ovarian tissues and in ovarian cancer will likely provide new targets for diagnosis and therapy. Recently, much has been learned about the genes expressed in ovarian cancer through studies with cDNA arrays and serial analysis of gene expression. However, these methods do not allow highly quantitative analysis of gene expression on a large number of specimens. Here, we have used quantitative real-time RT-PCR in a panel of 39 microdissected ovarian carcinomas of various subtypes to systematically analyze the expression of 13 genes, many of which were previously identified as up-regulated in a subset of ovarian cancers by serial analyses of gene expression. The genes analyzed are glutathione peroxidase 3 (GPX3), apolipoprotein J/clusterin, insulin-like growth factor-binding protein 2, epithelial cell adhesion molecule/GA733-2, Kop protease inhibitor, matrix gla protein, tissue inhibitor of metalloproteinase 3, folate receptor 1, S100A2, signal transducer and activator of transcription 1, secretory leukocyte protease inhibitor, apolipoprotein E, and ceruloplasmin. All of the genes were found overexpressed, some at extremely high levels, in the vast majority of ovarian carcinomas irrespective of the subtype. Interestingly, GPX3 was found at much higher levels in tumors with clear cell histology and may represent a biomarker for this subtype. Some of the genes studied here may thus represent targets for early detection ovarian cancer. The gene expression patterns were not associated with age at diagnosis, stage, or K-ras mutation status in ovarian cancer. We find that several genes are coordinately regulated in ovarian cancer, likely representing the fact that many genes are activated as part of common signaling pathways or that extensive cross-talk exists between several pathways in ovarian cancer. A statistical analysis shows that genes commonly up-regulated in ovarian cancer may result from the aberrant activation of a limited number of pathways, providing promising targets for novel therapeutic strategies.
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PMID:Coordinately up-regulated genes in ovarian cancer. 1135 98

Cholesterol clearly plays an influential role in promoting the production of amyloid beta (Abeta) and possibly the progression of Alzheimer's Disease (AD). The AD Cholesterol-Lowering Treatment trial (ADCLT; 1 year duration) tested atorvastatin and found significant benefit on measures of cognition and depressive symptoms in treated patients (N = 32) compared to placebo (N = 31). We assessed the circulating levels of Abeta(1-40), Abeta(1-42), ceruloplasmin (copper chaperone), apolipoprotein E and HDL-cholesterol in blood collected at each clinical visit during the ADCLT. We also determined the circulating cholesterol, ceruloplasmin, and Abeta levels in AD and MCI (mild cognitive impairment) patients, and controls (two groups stratified by function; high and low) participating in our Brain Bank Program. Each Brain Bank individual was clinically assessed for performance on the Mini-Mental Status Exam (MMSE), Rey auditory verbal learning test (AVLT), Clock draw, and UPSIT (smell identification test). Among individuals of equal age and education, scores on the MMSE were significantly reduced in AD compared to both MCI and controls, as were scores on the UPSIT. Ability on delayed verbal recall was significantly reduced in AD compared to MCI, and in MCI compared to both control groups. Performance on the Clock draw was similar for AD and MCI patients, but was significantly reduced when comparing MCI to control. Both cholesterol and ceruloplasmin levels were significantly increased in low-function controls compared to the high-function control group, but were not different from levels identified in the MCI and AD patients. Significantly increased levels of Abeta(1-40) occurred in low- compared to high-function controls, with a further significant increase in MCI compared to low-function controls. Circulating Abeta(1-40) levels were decreased in AD compared to MCI. Levels of Abeta(1-42) were not significantly different between the groups. The slight gradual increase in circulating Abeta(1-40) and Abeta(1-42) levels produced by atorvastatin treatment in the ADCLT were not significant compared placebo. There was a trend for significant reduction in circulating ceruloplasmin levels after a year of atorvastatin therapy compared to levels observed at screen. The levels of HDL-cholesterol remained stable in the atorvastatin treated AD patients for 9 months and then decreased significantly compared to the placebo group at the 1-year time-point. The combined data support a role for cholesterol in AD and a possible influence of increasing circulating copper levels. The deterioration of function in controls and transition to MCI may be associated with concomitant incremental increases in circulating Abeta(1-40) levels. Increased cholesterol and ceruloplasmin levels may be associated with slight deterioration in function among controls as a precursor to impairment considered MCI. The clinical benefit of atorvastatin therapy is clearly not associated with decreased circulating Abeta or increased HDL-cholesterol, but a positive influence of reduced copper (ceruloplasmin) levels may be a consideration.
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PMID:Cholesterol, copper and Abeta in controls, MCI, AD and the AD cholesterol-lowering treatment trial (ADCLT). 1637 52

Prospective studies have demonstrated that an imbalance between oxidative damage and antioxidative protection can play a role in the development and progression of atherosclerosis. Also, genotypes with the apolipoprotein E epsilon4 allele have been associated with an increase risk for this pathology. Based on this knowledge, the aim of this study was to evaluate indicators of the redox balance, trace elements, and apolipoprotein E allelic profile in subjects from the Lisbon population with clinically stable atherosclerosis, at risk for atherosclerotic events, and in healthy subjects for comparison. The activities of superoxide dismutase in erythrocytes and glutathione peroxidase in whole blood, plasma total thiols, and serum ceruloplasmin were kept unchanged among the three groups. Serum alpha- tocopherol was increased in atherosclerotic patients. Total malondialdehyde in serum and protein carbonyls in plasma, which are indicators of lipid and protein oxidative damage, respectively, reached their highest values in risk subjects. The concentrations of potassium and calcium, in plasma and in blood cells, were slightly elevated in patients and might reflect an electrolytic imbalance. Regarding the apolipoprotein E polymorphism, atherosclerotic patients had an increased incidence of the high-risk genotypes for atherogenesis (epsilon3/epsilon4 and epsilon4/epsilon4). A multivariate model applied to the general population using most of the parameters clearly separated the three groups at study (i.e., the healthy group from the steady-state group of risk disease and from the atherosclerotic one). As shown by us, the usefulness of biochemical and complementary genetic markers is warranted for a better knowledge on atherosclerosis molecular basis.
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PMID:Systemic markers of the redox balance and apolipoprotein E polymorphism in atherosclerosis: the relevance for an integrated study. 1694 16

To search out novel biomarkers for monitoring diabetes prognosis, we examined the effect of hypoglycemic fungal exopolysaccharides (EPS) on the differential levels of plasma proteins in streptozotocin-induced diabetic rats. The orally administrated EPS exhibited an excellent hypoglycemic effect, lowering the average plasma glucose level, and increasing insulin secretion in diabetic rats. The 2-DE analysis of rat plasma demonstrated that about 500 visualized spots were differentially regulated, of which 20 spots were identified as principal diabetes-associated proteins. The distinct effect of diabetes induction on the pattern of rat plasma proteins includes the down-regulation of albumin, apolipoprotein E (Apo E), alpha1-inhibitor-3, fetuin beta, Gc-globulin, hemopexin, vitronectin, and transthyretin (TTR) monomer, and the up-regulation of Apo A-I, Apo A-IV, ceruloplasmin, alpha1-antitrypsin, serine protease inhibitor III, and transferrin. Those protein levels were interestingly restored to those of healthy rats by EPS treatment, although the order of magnitude of the changes differed widely. Two proteins of interest showed distinct differential expression with opposite trends: TTR tetramer was significantly down-regulated and immunoglobulin (Ig) kappa light chain was significantly up-regulated upon diabetes induction, both of which were also normalized to those of healthy groups after EPS treatment.
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PMID:Effect of fungal polysaccharides on the modulation of plasma proteins in streptozotocin-induced diabetic rats. 1694 19

Non-ceruloplasmin bound copper ('free') seems slightly elevated in Alzheimer's disease (AD) patients. To test the hypothesis of a correlation between 'free' copper and liver function in AD. We evaluated 51 AD patients and 53 controls through typical tests for chronic liver disease (AST, ALT, gamma-GT, Albumin, prothrombin time - PT-, bilirubins), along with copper, ceruloplasmin, iron, cholesterol in the serum and apolipoprotein E epsilon4 (APOE4) genotype. Absolute serum copper and 'free' copper were higher, albumin was lower and PT longer in AD patients than in controls. 'Free' copper correlated negatively with markers of liver function, in that albumin and albumin/PT ratio (r = -0.43, p = 0.004), and positively with direct bilirubin. Copper and 'free' copper were higher in the APOE4 carriers. These results suggest that abnormalities in copper metabolism might have an effect on liver function in AD.
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PMID:'Free' copper in serum of Alzheimer's disease patients correlates with markers of liver function. 1764 16

Since many years the apolipoprotein E epsilon4 allele (APOE-epsilon4) is known to be associated with Alzheimer disease (AD) but the mechanisms of these associations remained unclear. In the last years, the potential pathogenetic role of 'free' copper (i.e. non-ceruloplasmin bound copper) has been evidenced in AD. Recently, elevated 'free' copper was found to be correlated with slowing of cortical electroencephalographic (EEG) rhythms. The present work aimed to check the hypothesis that the strength of the correlations between free-copper and alterations of cortical rhythms might be different in carriers and non-carriers of the APOE-epsilon4 allele. Fifty-four AD patients and 20 healthy controls were included in the study. In all of them 1) APOE genotyping was performed; 2) total serum copper and ceruloplasmin was determined in order to calculate the serum 'free' copper; and 3) resting eyes-closed EEG rhythms were recorded and spectral brain activity was estimated via LORETA. A 'two correlation coefficients comparison' test was used to test the strength of the correlation in APOE-epsilon4 carriers and non-carriers. 'Free' copper levels were higher in patients than in controls and correlated positively with parietal-temporal delta and negatively with parieto-temporal alpha-1 activities. The correlation between 'free' copper and temporal alpha-1 activity was stronger in APOE-epsilon4 carriers than in non-carriers. Peroxide levels correlated with higher temporal delta in the AD group. APOE-epsilon4 appears to modulate the effect of copper on the altered AD brain activities, suggesting that modulation of oxidative stress related to copper dysfunction may be one of the mechanisms that make APOE-epsilon4 a risk factor for AD.
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PMID:An observational study on the influence of the APOE-epsilon4 allele on the correlation between 'free' copper toxicosis and EEG activity in Alzheimer disease. 1848 14

There is currently considerable interest in the potential health benefits of isoflavones in functional foods and in the future prospects for the development of new products of benefit to the consumer. The potential health benefits of isoflavones may include protection against age-related diseases including cardiovascular disease, osteoporosis, hormone-dependent cancer and loss of cognitive function. The mechanisms involved may include weak oestrogenic action and antioxidant activity. Our proteomic investigations of changes in the human serum profile in response to the consumption of isoflavones in soya functional foods suggest potentially beneficial modulation of the levels of a number of serum proteins, including increased apolipoprotein E (involved in lipid metabolism) and caeruloplasmin (antioxidant and copper regulatory properties) levels and decreased alpha-1-acid glycoprotein (involved in immunomodulation) levels that may contribute to vascular protection. Furthermore, preliminary metabonomic data indicates an alteration in the urinary metabolite profile after isoflavone consumption, which may be of significance.
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PMID:Health benefits of isoflavones in functional foods? Proteomic and metabonomic advances. 1881 37


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