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)

Ceruloplasmin (CP) is a plasma glycoprotein that transports copper throughout the body. In previous studies (Yang, F., Naylor, S., Lum, J., Cutshaw, S., McCombs, J., Naberhaus, K., McGill, J., Adrian, G., Moore, C., Barnett, D., and Bowman, B. (1986) Proc. Natl. Acad. Sci. U. S. A. 83, 3277-3261), two CP cDNA clones, CP-1 and CP-2, from a human cDNA library, differed from each other by the presence or absence, respectively, of 12 nucleotide bases encoding a deduced sequence of Gly-Glu-Tyr-Pro near the carboxyl-terminal region of the ceruloplasmin molecule. Examination of genomic DNA demonstrates that the two CP mRNAs are produced from a single gene by alternative spliced patterns. The additional amino acids deduced in CP-1 are products of alternative splicing within an intron of the CP gene at a site 12 nucleotide bases 3' to the commonly used site of CP-2. The CP-1 mRNA transcript encoding four extra amino acids appeared as a minor species accompanying CP-2 mRNA in placenta and chondrocytes. CP-1 mRNA was the predominant CP transcript in a lymphoblastic leukemia cell line, CEM. The mRNA examined from other tissues contained only CP-2 mRNA transcripts. These findings predict that alternative RNA splicing may lead to the differential expression of CP genomic sequences and produce alternate isoforms from a single CP gene in specific tissues.
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PMID:Human ceruloplasmin. Tissue-specific expression of transcripts produced by alternative splicing. 235 23

Ceruloplasmin is a copper containing serum glycoprotein. It is an acute-phase protein and its levels are increased in inflammation and in a number of experimental and human tumors. It is normally synthesized in the liver and not in fibroblasts. In this paper we present evidence that ceruloplasmin mRNA is synthesized in Balb/C 3T3 cells and its levels are increased about 3-fold in Rous-Sarcoma virus (RSV) transformed cells. The ceruloplasmin mRNAs from rat liver and RSV 3T3 cells have the same electrophoretic mobility.
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PMID:Induction of the ceruloplasmin mRNA in Balb/C 3T3 cells after Rous-Sarcoma virus transfection. 243 32

Bronchoalveolar lavage fluid (BALF) was analysed to obtain information on leakage of proteins from the blood into the respiratory lumen and on local synthesis. Albumin, ceruloplasmin and alpha-2-macroglobulin were measured in paired BALF and serum samples from patients with acute pneumonitis or asthma. Ceruloplasmin (CP) and alpha-2-macroglobulin (A2M) were measured by ELISAs thereby avoiding concentration of BALF. The quotients 10(3) ([protein]BALF)/(protein]serum), Qprotein, were calculated as well as the relative coefficients of excretion, RCE: Qprotein/Qalbumin. The QCP and QA2M increased parallel to Qalbumin in patients with pneumonitis and QCP increased parallel with Qalbumin in the asthma patients. This indicates that abnormal leakage of proteins from the blood rather than local synthesis cause the increased concentrations of these proteins in the BALF. Increased values for the RCE of CP and A2M were observed at normal Qalbumin. We therefore conclude that the determination of CP and A2M yields more detailed information on leakage of proteins from the blood into the airway compartment than that of albumin.
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PMID:ELISA of ceruloplasmin and alpha-2-macroglobulin in paired bronchoalveolar lavage fluid and serum samples. 244 79

Because a number of different cytokines have been reported to regulate the synthesis of human, murine, and rat acute phase proteins (APP), we studied the effect of cytokines on production of several major human APP in a single system, the human hepatoma cell line Hep 3B. Conditioned medium (CM) prepared from human blood monocytes activated with LPS in the presence of dexamethasone led to substantial induction of serum amyloid A (SAA) and C-reactive protein (CRP) synthesis whereas the defined cytokines IL-1 beta, TNF alpha, and medium from a human keratinocyte cell line (COLO-16), containing hepatocyte-stimulating factor activity, failed to induce these two major APP. Induction of SAA and CRP was accompanied by an increase in concentration of their specific mRNA. Size fractionation of CM from activated monocytes by fast protein liquid chromatography indicated that SAA- and CRP-inducing activity eluted as a single peak with a Mr of approximately 18 kDa. alpha 1-Antitrypsin, which also failed to respond to IL-1 beta or TNF alpha, was induced by both CM and medium from COLO-16 cells. The induction of AT by CM was accompanied by an increase in specific mRNA. Induction of ceruloplasmin and alpha 1-antichymotrypsin and decrease in the synthesis of albumin was achieved by both CM and IL-1 beta. Ceruloplasmin and albumin responded in a comparable fashion to both TNF alpha and medium from COLO-16 cells; the response of ACT to these cytokines was not evaluated. These results indicate that human SAA and CRP are induced in Hep 3B cells by products of activated monocytes but not by IL-1 beta, TNF-alpha, or some hepatocyte-stimulating factor preparations and that a group of heterogeneous mechanisms are involved in the induction of the various human APP.
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PMID:Heterogeneous nature of the acute phase response. Differential regulation of human serum amyloid A, C-reactive protein, and other acute phase proteins by cytokines in Hep 3B cells. 245 96

The influence of ceruloplasmin on the development of delayed hypersensitivity (DHS) and activity of T-suppressors were studied in experiments on intact Balb/c mice. Ceruloplasmin introduced in a dose of 5 mg per 1 kg of weight a day before immunization of animals is shown to have a stimulating effect. The amount of the introduced drug being raised to 200 mg per 1 kg of weight suppressed the ability of organism to form DHS effect rather than increased it. Ceruloplasmin is stated to inhibit induction of DHS suppressors and to exert no effect on the expression of functional activity of the formed suppressors.
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PMID:[The activating effect of ceruloplasmin on the development of delayed hypersensitivity in mice]. 252 45

Cancer of the gastrointestinal tract (GIT) is very commonly encountered in Kashmir Valley of India. Serum copper and ceruloplasmin levels were investigated in 75 patients with GIT cancer, 42 non-GIT cancer and 75 normal healthy controls. The mean serum copper in the control group was 1,078 (S.D. 0,296) mg/L, while in patients with GIT and non-GIT cancers, it was 1,738 (S.D. 0,675) and 1,449 (S.D. 0,501) mg/L. Copper in both types of cancers showed significant increase (p less than 0.001). It was significantly higher in GIT cancers (p less than 0.01) as compared to non-GIT cancers. Ceruloplasmin in controls was 379 (S.D. 51) mg/L, while in GIT and non-GIT cancer patients the values were 363 (S.D. 75) and 364 (S.D. 77) mg/L, respectively. No significant difference could be found in either of the groups. In Kashmir Valley, the copper content in body tissues is likely to be on the high side because copper utensils are widely used by the general population. Water and milk samples stored in copper vessels and salt tea prepared in copper vessels showed markedly high levels of copper.
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PMID:Serum copper levels in gastrointestinal tract (GIT) cancer. 253 34

The plasma protein, ceruloplasmin, has been implicated as an anti-inflammatory agent, although this property has not been demonstrated unequivocally in vivo. The role of this protein in an in vitro system of cultured endothelial cells and polymorphonuclear leukocytes (PMNs) was investigated. One of the initial steps in an inflammatory response is increased adhesion between PMNs and the endothelial lining of the blood vessels. The results showed that ceruloplasmin interferes with this process and reduces the number of phorbol myristate acetate-activated leukocytes that adhere to endothelium. Preincubation of either the activated PMNs or the endothelium with ceruloplasmin did not produce the same results, suggesting that the continuous presence of ceruloplasmin is required. During attachment PMNs become activated and release a variety of substances, including toxic oxygen species such as superoxide and hydrogen peroxide. In the in vitro system used in this study no injury occurred to the endothelial cells, as measured by 51Cr release, when activated PMNs were added with ceruloplasmin. The data show that ceruloplasmin reduced, in a dose dependent manner, the levels of superoxide produced by the activated PMNs, further supporting ceruloplasmin's previously reported role as a scavenger of superoxide. Ceruloplasmin also reduced the levels of superoxide when activated PMNs were in contact with endothelial cells. Although ceruloplasmin interfered with the copper-dependent scavenger enzyme, superoxide dismutase (SOD), in a cell-free system, ceruloplasmin had no effect on SOD in intact endothelial cells. These results suggest that ceruloplasmin may act as an anti-inflammatory agent by reducing the number of PMNs attaching to endothelium and by acting as an extracellular scavenger of superoxide.
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PMID:Ceruloplasmin reduces the adhesion and scavenges superoxide during the interaction of activated polymorphonuclear leukocytes with endothelial cells. 255 11

The antioxidant enzyme ceruloplasmin effect on the state of lipid and peroxide metabolism in rats with alimentary hypercholesterolemia was studied. Ceruloplasmin was found to inhibit the development of hyperlipoproteinemia, to decrease the level of free-radical oxidation of lipids and to increase the antioxidant demands of tissues. The observed effects could be explained by the antioxidant properties of ceruloplasmin.
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PMID:[Lipid free-radical oxidation in rats with alimentary hypercholesterolemia and its correction with ceruloplasmin]. 262 52

Ceruloplasmin binds to the membranes of K562 cells. The binding has been shown to result in a temperature-dependent transfer of ceruloplasmin-bound copper into the cytosol. Ascorbic acid (100 microM) stimulates the transmembrane transfer nearly 10-fold, depending on the initial concentration of 67Cu-ceruloplasmin. The protein moiety of ceruloplasmin does not enter the cells. Bathocuproine disulfonate, a chelator specific for cuprous copper, inhibits the uptake, suggesting copper atoms are reduced concomitant with their removal from ceruloplasmin. Cytosolic 67Cu from ceruloplasmin was found mainly bound to Cu, Zn superoxide dismutase, the major cytosolic copper protein in these cells. Evidence supporting the various phases in the ceruloplasmin-mediated transport mechanism are presented.
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PMID:Copper transport: insights into a ceruloplasmin-based delivery system. 262 93

The paper presents the results of kinetic studies covering the reactions with the participation of two enzymes belonging to the group of "blue oxidases"--ascorbate oxidase and ceruloplasmin. Using variable physico-chemical parameters of reactions such as: temperature, presence of denaturizing factors, various substrates, it was possible to draw conclusions as to the structure and mechanism of reactions catalyzed by these enzymes. The following findings were established: 1. Ceruloplasmin is characterized by the absence of quarternary structure and lesser substrate specificity as compared with ascorbate oxidase. 2. The mechanism of reactions catalyzed by ceruloplasmin and ascorbate oxidase is different, probably due to the fact that there is no typical active centre binding the substrate in ceruloplasmin. 3. The application of variable parameters of physico-chemical reactions in the kinetic studies facilitates the description of the structures of enzymes and the mechanism of reactions being catalyzed by them.
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PMID:[Effect of selected physico-chemical parameters on changes in ascorbate oxidase and ceruloplasmin activities]. 263 99


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