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At least 19 recordsLinked to original sources
PubMed1992

Rat ceruloplasmin: resistance to proteolysis and kinetic comparison with human ceruloplasmin.

Rat ceruloplasmin was purified from serum using fast protein liquid chromatography and compared to human ceruloplasmin isolated in the same manner. Rat ceruloplasmin was found to be more resistant to plasmin-mediated proteolysis than was human ceruloplasmin. Although both proteins were cleaved initially to products with apparent molecular weights of 116,000 and 20,000 Da, rat ceruloplasmin was resistant to further proteolysis, whereas the human enzyme was cleaved to smaller fragments. Primary structure differences could account for the different relative stabilities between the two enzymes. Kinetic analysis of rat ceruloplasmin produced a biphasic v vs v/s plot with apparent Km's of 40 and 1.5 microM for iron. When compared with the human enzyme, rat ceruloplasmin showed about one-fourth the ferroxidase activity and had a much broader pH profile than that of human ceruloplasmin. Rates of p-phenylenediamine oxidation by rat ceruloplasmin were about one-half those obtained with human ceruloplasmin, with maximal p-phenylenediamine oxidase activity at pH 5.0 for both enzymes.

Amino Acid Sequence↗
PubMed1993

Inhibition of the copper incorporation into ceruloplasmin leads to the deficiency in serum ceruloplasmin activity in Long-Evans cinnamon mutant rat.

Although ceruloplasmin is known to be a copper-transporting protein, little is known about the biochemical mechanisms of copper incorporation into ceruloplasmin during the biosynthesis. We have examined various levels of ceruloplasmin biosynthesis in the Long-Evans Cinnamon (LEC) rat, which possesses a mutation causing the deficiency in serum ceruloplasmin activity associated with excess hepatic copper accumulation. Southern and Northern blot analyses revealed that the gene and mRNA encoding ceruloplasmin resided normally in LEC rat liver. Western blot analysis showed a normal level of ceruloplasmin in LEC rat serum. Following metabolic labeling of hepatocytes with 64Cu, no radioactive copper was detected in the ceruloplasmin fraction in LEC rat hepatocytes using Sephadex G-75 column chromatography, indicating that copper incorporation into ceruloplasmin is deficient in the LEC rat. Furthermore, LEC rat hepatocytes incubated with 64Cu also showed a reduction in the efficiency of copper transport from cytosolic to noncytosolic fractions and a reduced copper efflux from the hepatocytes, indicating that LEC rat hepatocytes possess an abnormality in copper metabolism. These results suggest that an abnormality of the copper delivery mechanism causes an inhibition of copper incorporation into the ceruloplasmin molecule in the liver, leading to the deficiency in serum ceruloplasmin activity in the LEC rat. In addition, this abnormality also seems to cause an inhibition of biliary copper excretion. The blocking of these two copper exclusion pathways is thought to lead to excess hepatic copper accumulation in the LEC rat. Thus, the LEC rat should be a good model for studying the biochemical process responsible for copper delivery.

Animals↗
PubMed1992

Dolphin ceruloplasmin: the first proteolytically stable mammalian ceruloplasmin.

1. Ceruloplasmin, the blue protein of the plasma of vertebrates, was isolated from dolphin, a marine mammal. The protein showed overall physico-chemical parameters very similar to those of all other mammalian ceruloplasmins. The spectroscopic properties indicated a conservation of the copper binding sites. 2. Non-denaturing electrophoresis revealed a conformation similar to that of other mammalian ceruloplasmins. EPR spectroscopy and calorimetric analyses indicated a three-domain arrangement of the protein typical of "aged" ceruloplasmin. 3. Dolphin ceruloplasmin is the only mammalian ceruloplasmin insensitive to trypsin, plasmin or chymotrypsin. This property, however, does not result in a higher conformational stability of the molecule. Thus, susceptibility of ceruloplasmin to aging is not directly related to the lability to proteases, which is typical of all other mammalian ceruloplasmins so far studied.

Animals↗
PubMed1993

Serum ceruloplasmin, plasma copper concentration and copper to ceruloplasmin ratio in cervical carcinoma.

Several studies have shown that plasma/serum copper and ceruloplasmin concentrations are increased in various carcinomas. We determined serum concentrations of ceruloplasmin and plasma copper concentration to evaluate the clinical usefulness of these tests in patients with cervical carcinomas. There was a significantly higher ceruloplasmin concentration in patients with cervical carcinoma compared to healthy controls. Plasma concentrations of copper were not significantly different in the two groups of subjects. The copper to ceruloplasmin ratio was lower in cancer patients than in control subjects. There was a significant increase in the serum concentrations of ceruloplasmin with increasing FIGO stage of cancer. Copper concentration in advanced tumours (FIGO stage 3) were significantly higher compared to control subjects or FIGO 1 and 2. Copper to ceruloplasmin ratio was lower in FIGO stage 2 and 3 patients compared to stage 1 or control subjects. Ceruloplasmin can also discriminate between large tumours which are inoperable and early cervical carcinomas better than copper or copper to ceruloplasmin ratio.

Adult↗
PubMed1981

Electron paramagnetic resonance study of storage effects on ceruloplasmin in human serum compared with purified ceruloplasmin in aqueous solution.

The EPR signal amplitude of human serum ceruloplasmin shows significant changes as a function of time and temperature during storage. The same behavior occurs with aqueous solutions of purified ceruloplasmin. From the observation that the spectral lines of the EPR signal of ceruloplasmin from unmanipulated serum are identical to those coming from purified ceruloplasmin, we conclude that only type I Cu2+ of ceruloplasmin are involved in the signal changes. A temperature-dependent electron shift toward type I Cu2+ paramagnetic centers, occurring via the type II and type III Cu2+ species of the protein, is believed responsible for the process. The possible origin of the reducing electrons is discussed. A procedure to obtain reproducibility of recording of EPR spectra of ceruloplasmin in physiological fluids is proposed.

Blood↗
PubMed1999

Investigation of the anomalous spectroscopic features of the copper sites in chicken ceruloplasmin: comparison to human ceruloplasmin.

Chicken ceruloplasmin has been previously reported to display a number of key differences relative to human ceruloplasmin: a lower copper content and a lack of a type 2 copper signal by electron paramagnetic resonance (EPR) spectroscopy. We have studied the copper sites of chicken ceruloplasmin in order to probe the origin of these differences, focusing on two forms of the enzyme: "resting" (as isolated by a fast, one-step procedure) and "peroxide-oxidized". From X-ray absorption, EPR, and UV/visible absorption spectroscopies, we have shown that all of the copper sites are oxidized in peroxide-oxidized chicken ceruloplasmin and that none of the type 1 copper sites display the EPR features typical for type 1 copper sites that lack an axial methionine. In the resting form, the type 2 copper center is reduced. Upon oxidation, it does not appear in the EPR spectrum at 77 K, but it can be observed by using magnetic susceptibility, EPR at approximately 8 K, and magnetic circular dichroism spectroscopy. It displays unusually fast relaxation, indicative of coupling with the adjacent type 3 copper pair of the trinuclear copper cluster. From reductive titrations, we have found that the reduction potential of the type 2 center is higher than those of the other copper sites, thus explaining why it is reduced in the resting form. These results provide new insight into the nature of the additional type 1 copper sites and the redox distribution among copper sites in the different ceruloplasmins relative to other multicopper oxidases.

Animals↗
PubMed1980

Purification of rat ceruloplasmin. characterization and comparison with human ceruloplasmin.

Rat ceruloplasmin was purified by a three-step column chromatography procedure, utilizing DEAE-Sepharose, Sepharose CL-6B, and CM-Sephadex A50 columns. The molecular weight of rat ceruloplasmin determined by a molecular sieve column was 124,000 daltons. An optical density ratio (610 nm/280 nm) of 0.051 and a molar extinction coefficient of 8600 were obtained. A decrease in lysine in rat ceruloplasmin compared with human ceruloplasmin could account for its reduced anodal mobility. Other differences in the amino acid sequence of the rat ceruloplasmin included an increase in methionine and cystine/cysteine, and a decrease in histidine, tyrosine and tryptophan.

Amino Acids↗
PubMed1985

Reaction of human ceruloplasmin and anion treated ceruloplasmin with diethyldithiocarbamate.

The reaction of human ceruloplasmin and anion treated ceruloplasmin with diethyldithiocarbamate was studied at pH 5.5. The analysis of optical and EPR spectra at 9 GHz showed that ceruloplasmin contains five paramagnetic copper ions, two of which, X and Y, not involved in enzymatic activity, are chelated by diethyldithiocarbamate; the complex thus formed is easily removed by high-speed centrifugation. However, the enzyme depleted of these two X and Y copper ions is able to compete with the Cu(II)-diethyldithiocarbamate complex, as time elapses, recovering both Cu(II) atoms. In addition diethyldithiocarbamate acts as a reducing agent for the two type-I copper atoms when added in large excess to the enzyme or the anion treated enzyme.

Anions↗
PubMed1998

A novel splicing mutation in the ceruloplasmin gene responsible for hereditary ceruloplasmin deficiency with hemosiderosis.

Hereditary ceruloplasmin deficiency with hemosiderosis (aceruloplasminemia) is a newly recognized autosomal recessive disorder of copper-iron metabolism due to mutations in the ceruloplasmin (Cp) gene. We report here a novel mutation in the Cp gene in a 54-year-old Japanese woman with this disease. She showed clinical triad; diabetes mellitus, retinal degeneration and neurological disorder in her middle age. Laboratory findings were characteristic for no detectable serum ceruloplasmin and increased serum ferritin. Liver biopsy revealed excessive storage of iron in hepatocytes and magnetic resonance imaging of the brain was indicative of increased iron content in the basal ganglia, thalamus and dentate nucleus. The a-->g substitution at the splice acceptor site of the intron 6 (1209-2) caused a 8-bp deletion in Cp mRNA by defective splicing, resulting in a premature termination codon at the amino acid position 388. Truncation of Cp, even if effectively translated, may cause loss of its normal function because of drastic change in its triangular structure.

Alternative Splicing↗
PubMedDate not supplied

Interaction between ceruloplasmin and Sendai virus envelope components. Note VI. Effect of ceruloplasmin on the antigenicity of Sendai virus and subviral fractions.

The results obtained by immunization of rabbits with different Sendai virus antigens (whole virus, envelope fragments and partially purified nucleoprotein) previously incubated with homologous ceruloplasmin confirm the hypothesis of a common protein support for both hemagglutinin and neuraminidase activities, demonstrate the participation of ceruloplasmin in the immune mechanism and reveal the role of the carbohydrate moiety of the glycoprotein in immune response. The probable mechanism of interaction between ceruloplasmin and Sendai virus envelope glycoprotein is discussed.

Animals↗
PubMedDate not supplied

The effect of ceruloplasmin on the multiplication and on some biological and physico-chemical characteristics of influenza virus A/PR8/34 (H0N1) cultivated on chorioallantoic membrane fragments. Note 1. Kinetics of virus multiplication and of some biological characteristics in the presence and absence of ceruloplasmin.

The presence of ceruloplasmin in the inoculum inhibits the multiplication of influenza virus A/PR8/34 (H0N1) in chorioallantoic membrane fragments. Virus corpuscles that remain uncoupled to ceruloplasmin infect the host cells and their replication results in progens whose properties differ from those of controls inoculated in the absence of ceruloplasmin. The variation in time of the characteristics of the respective virus progens is discussed.

Allantois↗
PubMed1995

A nonsense mutation of the ceruloplasmin gene in hereditary ceruloplasmin deficiency with diabetes mellitus.

A novel mutation of the ceruloplasmin (Cp) gene was found in a patient with hereditary ceruloplasmin deficiency (HCD) with diabetes mellitus (DM). The patient had been treated for DM for about 13 years, and then his illness was diagnosed as HCD. One year later, he was found dead in his home. A decrease in insulin-immunostained cells was observed in the islets of the patient's pancreas tissue, which accounted for his DM. The polymerase chain reaction (PCR)-direct sequencing analysis of the Cp gene of his daughter revealed a novel point mutation, G to A, at nucleotide 2630 in exon 15. This mutation changes the Trp858 codon (TGG) to a stop codon (TAG) (nonsense mutation). PCR-restriction analysis for the mutation revealed that the patient as well as his daughter was a heterozygote for the mutation, indicating that the patient was a compound heterozygote.

Amino Acid Sequence↗
PubMed2000

A novel mutation of the ceruloplasmin gene in a patient with heteroallelic ceruloplasmin gene mutation (HypoCPGM).

We found a novel missense mutation in the ceruloplasmin (Cp) gene in a patient with the heteroallelic Cp gene mutation (HypoCPGM). The patient was a 72-year-old woman who came to our hospital with a 1-year history of postural tremor of the hands. The diagnosis was made based on serum Cp and copper readings which were about half the normal levels, as well as MRI tests of her brain which showed characteristics for hereditary ceruloplasmin deficiency (HCD), known to be caused by the homoallelic Cp gene mutation. Polymerase chain reaction (PCR)-direct sequencing analysis of the Cp gene of the patient revealed a novel point mutation, A to T, at nucleotide position 82 in Exon 1. This mutation changes the Ile28 codon (ATT) to a Phe codon (TTT) (missense mutation). PCR-restriction analysis with restriction enzyme Tsp EI for the mutation revealed that both the patient and her son were heterozygotes for the mutation.

Aged↗
PubMed1985

Role of ceruloplasmin in inflammation: increased serum ceruloplasmin levels during inflammatory conditions and its possible relationship with anti-inflammatory agents.

Serum ceruloplasmin (CPN) levels under different types of acute and chronic experimentally-induced inflammatory conditions in rats and the effect of anti-inflammatory drugs viz. oxyphenylbutazone and hydrocortisone on serum CPN levels were investigated. Significant increase of serum CPN levels was observed in all experimental animal models with induced inflammatory conditions. Treatment with oxyphenylbutazone and hydrocortisone failed to inhibit the raised serum CPN levels. The concurrent increase of serum CPN level during induced inflammatory conditions suggest the involvement of serum CPN as one of the body's inbuilt defensive mechanism against noxious responses or inflammation. It is suggested that the increased serum CPN levels may be a complimentary factor associated with inflammatory conditions.

Animals↗
PubMed1984

Changes in functional ceruloplasmin concentrations of plasma and exudate and the effect of exogenous ceruloplasmin on the carrageenin-induced inflammation in rats.

Changes in functional ceruloplasmin (Cp) concentrations of plasma and exudate during acute and chronic inflammatory processes were studied in detail by measuring Cp oxidase activity in the carrageenin-induced inflammation in rats. In contrast with the plasma functional Cp level as an acute-phase reactant, the exudate functional Cp level was very low during the acute phase, increased in the chronic phase and reached a constant value which was only half value of the plasma functional Cp level. The locally injected Cp had no effect on the carrageenin-induced inflammation, suggesting that exogenous Cp has no anti-inflammatory effect on the inflamed rats eating normal diet.

Animals↗
PubMed1990

Molecular forms of ceruloplasmin in hepatolenticular degeneration and their interaction with human erythrocyte ceruloplasmin receptor.

Immunochemical methods were used to show that the sera of homozygous and heterozygous carriers of the Wilsonian gene contain, together with normal ceruloplasmin (CP), a CP-like protein that differs from CP in its enzymatic, immunological, and physicochemical properties. The CP-like protein was isolated from the sera of patients with hepatolenticular degeneration (HLD) by means of affinity chromatography, and monospecific antibodies to this protein were obtained. The presence of an 80 kDa immunoreactive polypeptide specific to the CP-like protein was demonstrated by immunoblotting with antibodies to normal CP and monospecific antibodies to the CP-like protein. Analysis of the ratios of the molecular forms of CP in homozygous and heterozygous carriers of the Wilsonian gene indicated that this ratio reflects the dosage of the mutant gene. The kinetic parameters of the interaction of these proteins with the CP-specific receptor on the erythrocyte membranes from healthy individuals and from patients with Wilson's disease (HLD) were determined. The CP receptor on erythrocyte membranes in HLD patients is not altered and its interaction with normal CP has the same kinetic parameters as the binding of normal CP to the erythrocyte receptors from healthy individuals. The CP-like protein also retains the ability to bind to the CP-specific receptor but the ligand-receptor complex is less stable than in the case of normal CP. The possible mechanism of the molecular heterogeneity of CP in the Wilsonian mutation is discussed.

Ceruloplasmin↗