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PubMed2006

Differential effects and changes of ceruloplasmin in the hippocampal CA1 region between adult and aged gerbils after transient cerebral ischemia.

In this study, we examined the differential effects and changes of ceruloplasmin between adult and aged gerbil hippocampus after transient forebrain ischemia. Ceruloplasmin in the hippocampal CA1 region of adult and aged gerbils was significantly changed after ischemia/reperfusion. Whereas, it was not significantly changed in the CA2/3 region compared to the CA1 region after ischemia. Ceruloplasmin immunoreactivity and its protein level in aged gerbil CA1 region were higher than those in adult gerbil CA1 region. Ceruloplasmin in the CA1 region was highest in adult gerbils and aged gerbils at 24h and 12h after transient ischemia, respectively. At these time points, strong ceruloplasmin immunoreactivity was observed in CA1 pyramidal cells. Thereafter, ceruloplasmin was decreased with time after ischemia. Four days after ischemia/reperfusion, ceruloplasmin immunoreactivity in both adult and aged gerbils was expressed in astrocytes in the CA1 region. Ceruloplasmin treatment in adult ischemic gerbils showed strong protective effect against ischemic damage in CA1 pyramidal cells compared to that in aged ischemic gerbils. We conclude that ceruloplasmin early increases in the aged gerbil CA1 region compared to that of the adult gerbil CA1 region may be associated with the earlier induction of reactive oxygen species, and ceruloplasmin shows strong neuroprotective effects in adults compared to those in aged gerbils.

Age Factors↗

PubMed2006

Plasma copper, iron, ceruloplasmin and ferroxidase activity in schizophrenia.

As ceruloplasmin and copper abnormalities have been implicated in schizophrenia, we investigated the role of a second copper-containing non-ceruloplasmin protein, the iron oxidase ferroxidase II, in a prospective study of ten inpatients with schizophrenia and a comparison group. Ferroxidase II is a protein known to reciprocally regulate with ceruloplasmin in Wilson's disease, an illness characterized by psychotic symptoms, decreased ceruloplasmin, and increased copper deposition in tissues. Ferroxidase II plays a key role in the maintenance of near-normal iron metabolism in Wilson's disease, but its role in schizophrenia has never been studied. In this study, we assayed ceruloplasmin by two enzymatic assays, a standard clinical laboratory p-phenylenediamine oxidation assay and a second assay based on the rate of the oxidation and incorporation of iron (Fe3+) into transferrin; we assayed ferroxidase II activity using this second iron oxidation assay. We found that ceruloplasmin levels as measured by both enzymatic methods, but not ferroxidase II, were elevated in schizophrenia. The increased ceruloplasmin also correlated with elevated serum copper as assayed by atomic absorption spectrophotometry, which was unsurprising as the majority of copper in blood is bound to ceruloplasmin. It has been proposed that copper, as a component of several enzymes linked to dopamine synthesis, may play a role in schizophrenia by exacerbating or perpetuating dopaminergic dysregulation. Our study suggests that the ceruloplasmin elevation in schizophrenia is specific, and not simply an elevation of plasma copper-containing oxidative enzymes. Increases in ceruloplasmin may result in increased levels of copper, which ultimately proves deleterious in schizophrenia.

Adult↗

PubMed2001

Copper, ceruloplasmin and superoxide dismutase (SOD1) in patients with Down's syndrome.

The aim of this study was primarily to investigate whether similar signs of copper dyshomeostasis occur in dementia with age in Down's syndrome as previously found in Alzheimer's disease. Copper was accordingly determined in plasma, ceruloplasmin concentration in serum, ceruloplasmin oxidative activity and ceruloplasmin specific oxidative activity (activity related to mass) in serum, and superoxide dismutase (SOD1) in erythrocytes in 35 (27 males, 8 females) 18-53 years old (average 37 years) patients with Down's syndrome (Down's patients) and their age- and gender-matched controls. SOD1 activity was on an average almost 50% higher in the patients than in their controls but the evidence of a causal relationship between increased SOD1 activity and Down's syndrome appears at best equivocal. Copper and ceruloplasmin levels and ceruloplasmin activities were similar in the patients and their controls. Ceruloplasmin and copper levels increased significantly with age in the patients but not in the controls. Ceruloplasmin activities or SOD1 activity did not change significantly with age, neither in the patients nor in the controls as whole groups. When SOD1 activity and ceruloplasmin activities of the oldest in the patients group (40 years or older) were compared with those of the younger patients, respectively, SOD1 activity and specific oxidative activity, but not ceruloplasmin oxidative activity were found to decrease significantly with age. The results thus suggest that development of dementia in Down's patients with age is paralleled with decrease in SOD1 activity and specific oxidative activity but not with decrease in ceruloplasmin oxidative activity itself as was also found in Alzheimer's patients.

Adolescent↗

PubMed2002

Elevated serum ceruloplasmin levels in subjects with metabolic syndrome: a population-based study.

Serum ceruloplasmin was reported to be an independent risk factor for cardiovascular disease. We investigated whether serum ceruloplasmin level is elevated in subjects with metabolic syndrome (MS, insulin resistance syndrome) in a community-based population. A total 883 subjects over 40 years of age were studied among a population of the Chongup district, a rural area of South Korea. Serum ceruloplasmin levels were measured, and oral glucose tolerance tests were performed. Known cardiovascular risk factors, such as serum lipids, fasting insulin level, and urinary albumin excretion rate (UAER), were also measured. Serum ceruloplasmin levels in the subjects with MS (n = 167, 325 +/- 141 mg/L) were significantly higher than in those without MS (278 +/- 93 mg/L, P <.001). The mean ceruloplasmin level also increased as the glucose tolerance worsened (278 +/- 95 mg/L in normal glucose tolerance [NGT], 303 +/- 108 mg/L in impaired glucose regulation, and 328 +/- 148 mg/L in diabetes; P <.001). Serum ceruloplasmin level was positively correlated with age, fasting glucose, postload 2-hour glucose, total cholesterol, triglyceride, systolic blood pressure, diastolic blood pressure, and UAER and negatively with high-density lipoprotein (HDL)-cholesterol. In multiple regression analysis, serum ceruloplasmin level was independently associated with age, fasting glucose, triglyceride, HDL-cholesterol, and UAER. In conclusion, serum ceruloplasmin level is elevated in the subjects with MS, as well as in subjects with impaired glucose regulation or diabetes mellitus. In addition, serum ceruloplasmin level is associated with various cardiovascular risk factors. These results suggest that elevated serum ceruloplasmin level can be a marker for metabolic stresses associated with MS.

Body Constitution↗

PubMedDate not supplied

[Age-related features of ceruloplasmin biosynthesis and distribution in rats].

Biosynthesis of ceruloplasmin, a copper-containing glycoprotein, which plays an important role in copper transfer and bidirectional iron transport in vertebrates, was studied in 7-day old rats characterized by the embryonic type of copper metabolism. In addition to the liver, copper is synthesized in the lungs, brain, and kidneys. The appearance of labeled ceruloplasmin in the blood flow coincides with the time of liberation of de novo synthesized ceruloplasmin from the liver. [14C]-Ceruloplasmin is absorbed from the blood flow by cells of the heart, lung, and kidneys and binds to erythrocytes. The polypeptide ceruloplasmin chain does not enter the brain cells from the blood flow. Immunoreactive polypeptides of the ceruloplasmin receptor were found using immunoblotting in plasma membranes of the heart, liver, kidneys, and erythrocytes, rather than in those of the brain. It was shown by reverse transcription coupled with PCR using selective primers these cells contain molecular forms of ceruloplasmin mRNAs programming the synthesis of both secretory ceruloplasmin and ceruloplasmin connected with the plasma membrane via the glycosyl phosphatidylinositol anchor. After transition to the adult type of copper metabolism, the blood serum contents of copper and ceruloplasmin sharply increase, while the content of CP in the cerebrospinal fluid, as measured according to the oxidase and antigen activities, and copper concentration, as determined by atom-absorption spectrometry, remain low. Ontogenetic features of the system ensuring the copper homeostasis in mammals are discussed.

Animals↗

PubMed2005

[Ceruloplasmin level of patients with liver disease in China].

OBJECTIVE: To find out the degree of overlap of ceruloplasmin concentration in patients presenting with liver disease, providing scientific evidences for the diagnosis and differential diagnosis of Wilson's disease (WD). METHODS: Measuring the serum ceruloplasmin concentration of patients presenting with liver diseases, all data were statistically analyzed with SPSS12 for Windows. RESULTS: The average serum ceruloplasmin concentration of patients with WD was (93.9 +/- 98.1) mg/L, which was significantly lower than patients with non WD. The ceruloplasmin concentration of 72.7% of patients with WD was less than 100 mg/L, and that of 42.9% of patients with WD was less than 50 mg/L, but the ceruloplasmin concentration of 9.1% of patients with WD was more than 210 mg/L. The average serum ceruloplasmin concentration of patients with acute hepatitis was (398.4 +/- 151.3) mg/L, which was significantly higher than other group. The average serum ceruloplasmin concentration of patients with severe hepatitis was (296.5 +/- 106.5) mg/L, which was significantly lower than other group. The ceruloplasmin concentration of 6.8% of patients with non WD was less than 210 mg/L, the lowest was 28 mg/L. CONCLUSIONS: There is some degree overlap in ceruloplasmin concentration between WD and other liver disease, WD could not be confirmed or excluded according to ceruloplasmin concentration only.

Ceruloplasmin↗

PubMed1990

Primary structure of rat ceruloplasmin and analysis of tissue-specific gene expression during development.

cDNA clones corresponding to rat ceruloplasmin were isolated from newborn rat lung and liver cDNA libraries and the nucleotide sequence was obtained. The derived amino acid sequence of rat ceruloplasmin is 93% homologous to the corresponding human sequence and contains a 19-amino acid leader peptide plus 1040 amino acids of mature protein. Southern blot analysis indicates that the ceruloplasmin gene exists as a single copy in the rat haploid genome. Using these cDNA clones in RNA blot analysis, a single 3.7-kilobase ceruloplasmin-specific transcript is detected in fetal rat liver and lung by day 15 of gestation. During fetal development the abundance of this transcript increases selectively in these two tissues and at birth is 60% of that found in the adult liver. Postnatally the temporal pattern of ceruloplasmin gene expression in lung and liver differs. Within the first 3 weeks postpartum ceruloplasmin mRNA content decreases in lung to undetectable levels, while that in the liver reaches adult levels. Primer extension reveals a single identical start site of ceruloplasmin gene transcription in lung and liver and biosynthetic studies indicate that each tissue synthesizes a ceruloplasmin protein which is qualitatively similar to that synthesized by adult liver. Ceruloplasmin mRNA is also detected in human fetal lung explant and a human lung adenocarcinoma cell line suggesting that a similar pattern of expression occurs in the developing human lung. These data indicate that lung is the predominant extrahepatic site of ceruloplasmin gene expression during fetal development and suggest that this protein may play a previously unappreciated role in lung development or pulmonary antioxidant defense.

Aging↗

PubMed1984

Ceruloplasmin. Increased serum concentration and impaired antioxidant activity in cigarette smokers, and ability to prevent suppression of elastase inhibitory capacity of alpha 1-proteinase inhibitor.

Bronchoalveolar lavage fluid of smokers and nonsmokers contains significant concentrations of ceruloplasmin, the major serum inhibitor of lipid peroxidation, with limited superoxide dismutase activity. This suggested that ceruloplasmin may protect the lower respiratory tract against oxidant(s) in cigarette smoke and air pollutants. We investigated (1) serum ceruloplasmin concentration and antioxidant activity (percentage inhibition of autoxidation of ox-brain homogenate) in healthy male and female smokers and nonsmokers, and (2) the capacity of ceruloplasmin to prevent suppression of the elastase inhibitory capacity of alpha 1-proteinase inhibitor by the oxidant chloramine T and by cigarette smoke solution. Mean ceruloplasmin concentration was 18% higher in 35 female smokers than in 46 male smokers (p less than 0.001), 17% higher in 22 female nonsmokers than in 18 male nonsmokers (p less than 0.005), 15% higher in the female smokers than in the female nonsmokers (0.02 greater than p greater than 0.01), and 14% higher in the male smokers than in the male nonsmokers (p less than 0.001). Serum antioxidant activity showed significant linear correlations with serum ceruloplasmin in smokers and nonsmokers of both sexes; correlation coefficients, all significant, ranged from 0.65 to 0.50. For comparable ceruloplasmin concentrations, serum antioxidant activity was significantly lower in smokers (males: 9%, p less than 0.001; females: 7%, 0.05 greater than p greater than 0.01) than in nonsmokers. There was a linear relationship between ceruloplasmin concentration and its ability to prevent suppression of the elastase inhibitory capacity of alpha 1-proteinase inhibitor by chloramine T and cigarette smoke solution. Our findings indicate: (1) that cigarette smoking can cause partial inactivation of serum antioxidant activity accompanied by insufficient compensatory increase in ceruloplasmin concentration, and (2) that ceruloplasmin may protect the lung against oxidant(s) in cigarette smoke and air pollutants.

Adult↗

PubMed1996

Relationship of obesity and body fat distribution with ceruloplasmin serum levels.

OBJECTIVE: To investigate the influence of obesity and body fat distribution on serum levels of ceruloplasmin, a risk factor for myocardial infarction. DESIGN: Fasting concentrations of ceruloplasmin, insulin, glucose, lipid pattern (cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides), blood pressure levels, and body fat distribution were determined in a population of non-diabetic subjects. SETTING: University Hospital Outpatient Clinic. SUBJECTS: 87 consecutive individuals (35 men and 52 women), represented by 27 normal weight (BMI: < 25.0), 20 overweight (BMI: > 25.0-30.0) and 40 obese (BMI: > 30.0) subjects. MEASUREMENTS: Serum insulin levels were quantified by radioimmunoassay, plasma glucose and lipid concentrations by enzymatic assays, and serum ceruloplasmin by nephelometry. Intra-abdominal thickness was measured by ultrasound technique. RESULTS: Ceruloplasmin levels were significantly (P < 0.001) higher in obese (36.5 +/- 8.60 mg/dl) than in overweight (30.4 +/- 6.17 mg/dl) and normal weight (29.3 +/- 8.06 mg/dl) subjects. Of several variables associated with ceruloplasmin (BMI, waist circumference, WHR, intra-abdominal thickness, triglycerides, cholesterol, LDL-cholesterol, insulin), only triglycerides (in both men and women) and ultrasound intra-abdominal thickness (in women) maintained a significantly independent relationship with this protein in multiple stepwise analysis. Moreover, both triglycerides and total cholesterol maintained an independent correlation with ceruloplasmin when the data from both men and women were pooled together. CONCLUSION: This study indicates that patients with central obesity have characteristically higher ceruloplasmin serum levels, and that ceruloplasmin concentrations are strongly correlated with serum triglyceride and cholesterol levels (in both sexes) and visceral fat accumulation (in women), independently of the other associated cardiovascular risk factors (insulin and blood pressure levels). Since ceruloplasmin has been shown to increase in response to the atherosclerotic inflammatory process, and to promote coronarosclerosis, the determination of serum ceruloplasmin in subjects with central obesity might be a useful tool to identify patients with the highest risk for myocardial infarction.

Adipose Tissue↗

PubMed1997

Stimulation of the ferroxidase activity of ceruloplasmin during iron loading into ferritin.

Ceruloplasmin purified from horse serum was rapidly reduced upon addition of increasing equivalents of ferrous iron, generating an electronically and conformationally distinct form. This form of ceruloplasmin was characterized by significant (80%) loss of EPR detectable type I and type II copper(II), complete loss of visible absorbance at 610 nm, as well as decreased hydrophobic surface area. The reduced form of ceruloplasmin slowly reduced molecular oxygen to complete its catalytic cycle. The presence of varied concentrations of apoferritin, but not apotransferrin, significantly enhanced the rate of ceruloplasmin oxidation. The magnitude of this stimulatory effect increased as the molar ratio of ceruloplasmin to apoferritin approached 1.0, shown previously to be the optimum ratio for loading iron into ferritin. The rate of ferrous iron oxidation by ceruloplasmin was significantly stimulated by the presence of apoferritin; however, apotransferrin had no effect. The length of time required for ceruloplasmin to oxidize all the iron and return to the native form of the enzyme was also affected by the concentration of iron. In addition, the rate of iron loading into ferritin was dependent upon ferrous iron concentration. These results provide evidence for the formation of a specific complex between the reduced form of ceruloplasmin and apoferritin and that reduction of ceruloplasmin by ferrous iron may be the signal for complex formation.

Animals↗

PubMed1998

Studies on the interaction between ferritin and ceruloplasmin.

We showed previously that ceruloplasmin associates with the H chain of rat liver ferritin during iron loading into ferritin such that the iron oxidized by ceruloplasmin was deposited into ferritin [S.-H. Juan et al. (1997) Arch. Biochem. Biophys. 341, 280-286]. Three synthetic decapeptides derived from domains 2, 4, and 6 of ceruloplasmin, referred to CP-2, CP-4, and CP-6, were utilized to identify a possible binding site on ceruloplasmin for ferritin. Two of the peptides, CP-4 and CP-6, were found to inhibit iron loading into the recombinant ferritin H chain homopolymer (rH-Ft) by ceruloplasmin. The extent of inhibition of iron loading into ferritin by ceruloplasmin by CP-6, but not CP-4, varied with pH, whereas the inhibitory effect remained constant in increasing concentrations of NaCl. The addition of rH-Ft quenched the fluorescence emission of CP-4 and CP-6, but not CP-2. The quenching of fluorescence was used to estimate dissociation constants for the peptides. Iron loading into ferritin in Hepes buffer was not affected in the presence of these peptides. In addition, synthetic peptides corresponding to the BC loop of ferritin H and L chains were utilized to localize an interaction site on ferritin for ceruloplasmin. The BC loop of H chain but not L chain of ferritin stimulated the ferroxidase activity of ceruloplasmin. Only the BC loop of ferritin H chain decreased the amount of iron loading into ferritin by ceruloplasmin.

Amino Acid Sequence↗

PubMedDate not supplied

Interaction of 125I-labelled ceruloplasmin with human trophoblast cells in vitro.

In vitro binding, internalization and release of the plasma protein ceruloplasmin was investigated using primary cultures of human placental trophoblast cells. Binding of 125I-labelled ceruloplasmin at 4 degrees C reached equilibrium by 5-6 h; binding was linear throughout all concentrations tested (1 nM-3.3 microM). Addition of greater than 5-10 microM unlabelled ceruloplasmin or a variety of other proteins (albumin, transferrin, IgG) were equally effective in displacing bound ceruloplasmin in a concentration-dependent manner. When cells were incubated at 37 degrees C, the majority of surface-bound 125I-labelled ceruloplasmin was released directly to the extracellular medium. Trypsin-resistant radioactivity increased to 18 per cent of initially bound ceruloplasmin within 1 min, declining to 5 per cent by 2 h. The acquisition of trypsin-resistant radioactivity was unaffected by the addition of a variety of metabolic inhibitors and no evidence of intracellular degradation of ceruloplasmin was found. In summary, our results suggest that the majority of ceruloplasmin binding to trophoblast cells is nonspecific, of low affinity, and easily dissociable at 4 degrees C. Only a small amount of ceruloplasmin appeared to be internalized, by an as yet unknown mechanism.

Ammonium Chloride↗

PubMed1999

The inhibition of myeloperoxidase by ceruloplasmin can be reversed by anti-myeloperoxidase antibodies.

BACKGROUND: The purpose of this study was to characterize the recently reported inhibition of myeloperoxidase (MPO) by ceruloplasmin and to determine whether this may be disturbed in the presence of anti-MPO antibodies. METHODS: Specificity of the binding between ceruloplasmin and MPO was confirmed by Western blotting and enzyme-linked immunosorbent assay (ELISA), and the enzymatic activity of MPO was measured in the presence of ceruloplasmin, affinity-purified anti-MPO antibodies, or both. The affinity of the binding between MPO and ceruloplasmin and MPO and the anti-MPO antibodies was measured using a biosensor, with the results confirmed by chaotrope ELISA. RESULTS: Affinity-purified anti-MPO antibodies from patients with microscopic polyangiitis and florid renal vasculitis inhibited the binding between ceruloplasmin and MPO to a maximum of 72.9 +/- 12.8%, whereas those from patients with Wegener's granulomatosis and only minimal renal involvement inhibited the binding to a maximum of only 36.8 +/- 10.9% (P < 0. 001), with comparable reversal of the ceruloplasmin-mediated inhibition of MPO activity. Measurement of the affinity of the interactions demonstrated that binding between MPO and the anti-MPO antibodies is stronger than that between MPO and ceruloplasmin (1.61 x 107 to 1.33 x 108 vs. 7.46 x 106 m-1), indicating that binding to the autoantibody would be favored in vivo. CONCLUSIONS: This study confirms a role for ceruloplasmin as a physiological inhibitor of MPO, and demonstrates how the inhibition may be disrupted in the presence of anti-MPO antibodies. Because a majority (16 of 21) of the antibodies did not themselves inhibit MPO activity, their interference with the inhibition mediated by ceruloplasmin may be brought about by steric hindrance consequent upon the binding of the antibody to a dominant epitope at or near the active site.

Adult↗

PubMed1996

Ceruloplasmin enhances smooth muscle cell- and endothelial cell-mediated low density lipoprotein oxidation by a superoxide-dependent mechanism.

Cultured vascular smooth muscle cells (SMC) and endothelial cells (EC) stimulate low density lipoprotein (LDL) oxidation by free radical-mediated, transition metal-dependent mechanisms. The physiological source(s) of metal ions is not known; however, purified ceruloplasmin, a plasma protein containing 7 coppers, oxidizes LDL in vitro. We now show that ceruloplasmin also increases LDL oxidation by vascular cells. In metal ion-free medium, human ceruloplasmin increased bovine aortic SMC- and EC-mediated LDL oxidation by up to 30- and 15-fold, respectively. The maximal response was at 100-300 microg ceruloplasmin/ml, a level at or below the unevoked physiological plasma concentration. Oxidant activity was dependent on protein structure as a specific proteolytic cleavage or removal of one of the seven ceruloplasmin copper atoms inhibited activity. Three lines of evidence indicated a critical role for cellular superoxide (O2.) in ceruloplasmin-stimulated oxidation. First, the rate of production of O2. by cells correlated with their rates of LDL oxidation. Second, superoxide dismutase effectively blocked ceruloplasmin-stimulated oxidation by both cell types. Finally, O2. production by SMC quantitatively accounted for the observed rate of LDL oxidation. To show this, the course of O2. production by SMC was simulated by repeated addition of xanthine and xanthine oxidase to culture medium under cell-free conditions. Neither ceruloplasmin nor O2. alone increased LDL oxidation, but together they completely reconstituted the oxidation rate of ceruloplasmin-stimulated SMC. These results are the first to show that ceruloplasmin stimulates EC- and SMC-mediated oxidation of LDL and that cell-derived O2. accounts quantitatively for metal-dependent, free radical-initiated oxidation of LDL by these cells.

Animals↗

PubMed2000

Site-directed mutagenesis of human ceruloplasmin:. production of a proteolytically stable protein and structure-activity relationships of type 1 sites.

A fully active recombinant human ceruloplasmin was obtained, and it was mutated to produce a ceruloplasmin stable to proteolysis. The stable ceruloplasmin was further mutated to perturb the environment of copper at the type 1 copper sites in two different domains. The wild type and the mutated ceruloplasmin were produced in the yeast Pichia pastoris and characterized. The mutations R481A, R701A, and K887A were at the proteolytic sites, did not alter the enzymatic activity, and were all necessary to protect ceruloplasmin from degradation. The mutation L329M was at the tricoordinate type 1 site of the domain 2 and was ineffective to induce modifications of the spectroscopic and catalytic properties of ceruloplasmin, supporting the hypothesis that this site is reduced and locked in a rigid frame. In contrast the mutation C1021S at the type 1 site of domain 6 substantially altered the molecular properties of the protein, leaving a small fraction endowed with oxidase activity. This result, while indicating the importance of this site in stabilizing the overall protein structure, suggests that another type 1 site is competent for dioxygen reduction. During the expression of ceruloplasmin, the yeast maintained a high level of Fet3 that was released from membranes of yeast not harboring the ceruloplasmin gene. This indicates that expression of ceruloplasmin induces a state of iron deficiency in yeast because the ferric iron produced in the medium by its ferroxidase activity is not available for the uptake.

Amino Acid Sequence↗

PubMed1999

Glycosyl phosphatidylinositol-anchored ceruloplasmin is expressed by rat Sertoli cells and is concentrated in detergent-insoluble membrane fractions.

The copper-binding protein, ceruloplasmin, is both a serum component and a secretory product of Sertoli cells. Studies on serum ceruloplasmin have demonstrated it to be a ferroxidase that is essential for iron transport throughout the body. We report here that a glycosyl phosphatidylinositol (GPI)-anchored form of ceruloplasmin is expressed by Sertoli cells. Sertoli cell GPI-anchored proteins were selectively released by phosphatidylinositol-specific phospholipase C and were analyzed by Western blotting. A 135-kDa band was identified as ceruloplasmin by multiple antibody recognition and by amino acid sequence analysis. The presence of the GPI anchor on ceruloplasmin was confirmed by Triton X-114 phase partitioning experiments and by recognition with an antibody to the GPI anchor. GPI-anchored ceruloplasmin was enriched in detergent-insoluble glycolipid-enriched membrane microdomains (DIGs) of Sertoli cells. This is the first report of GPI-anchored ceruloplasmin in Sertoli cells and the first study of GPI-anchored ceruloplasmin in DIGs. We suggest that GPI-anchored ceruloplasmin may be the dominant form expressed by Sertoli cells and that Sertoli cell DIGs may play a role in iron metabolism within the seminiferous tubule.

Animals↗

PubMed1987

Antioxidant activity of serum ceruloplasmin and transferrin available iron-binding capacity in smokers and nonsmokers.

We investigated in 39 healthy smokers (20 female, 19 male) and 38 healthy nonsmokers (18 female, 20 male): the impact of smoking and smoking-related factors on the concentration of serum ceruloplasmin, transferrin, transferrin available iron-binding capacity (AIBC), and serum antioxidant activity (AOA); the relative contribution of serum ceruloplasmin and AIBC to serum AOA; the association and possible interactive effects of serum ceruloplasmin, AIBC, and smoking with serum AOA; and the relation of pulmonary function in healthy smokers to serum AOA, ceruloplasmin, and AIBC. We found that: as compared with healthy nonsmokers, healthy smokers had higher serum ceruloplasmin concentration, similar serum transferrin and AIBC concentration, and lower serum AOA; ceruloplasmin, AIBC, and smoking acted additively, accounting for about 60% of the variability of serum AOA; the impact of AIBC on serum AOA was significantly greater than that of ceruloplasmin; and pulmonary function in the smokers was not significantly related to serum AOA, ceruloplasmin, or AIBC. Our findings suggest that: serum AIBC has a greater role in serum AOA than has previously been attributed to it; suppression of the AOA of serum constituent(s) other than those we measured may account for the significantly lower serum AOA in healthy smokers than in healthy nonsmokers; and normal air flow in healthy cigarette smokers is unrelated to serum AOA, ceruloplasmin, or AIBC concentration.

Adult↗

PubMed1987

Molecular studies of ceruloplasmin deficiency in Wilson's disease.

Deficiency of serum ceruloplasmin is a characteristic biochemical abnormality of Wilson's disease, although the mechanism of this finding is unknown. Ceruloplasmin messenger RNA (mRNA) levels were therefore examined in five patients with Wilson's disease and five controls with other types of hepatic disease. Northern and dot blot hybridizations showed that detectable ceruloplasmin mRNA was present in all of the patients with Wilson's disease, including one patient with no detectable serum ceruloplasmin. However, the ceruloplasmin mRNA levels in the Wilson's disease patients were only 33% that of controls (P less than 0.001). In contrast, albumin mRNA levels in the Wilson's disease patients averaged 161% that of controls. In an attempt to better delineate the level of gene expression responsible for this decrease in ceruloplasmin mRNA, the nuclear run-on assay was used to analyze transcriptional rates. The amount of ceruloplasmin gene transcription in four Wilson's patients was decreased to 44% that of three controls. These results indicate that the diminished serum ceruloplasmin levels in patients with Wilson's disease are due at least in part to a decrease in ceruloplasmin gene transcription.

Ceruloplasmin↗