Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have reported previously that the heavy chain of ferritin is required for iron incorporation by ceruloplasmin (J.-H. Guo, M. Abedi, and S. D. Aust (1996) Arch. Biochem. Biophys. 335(1)). The purpose of this study was to determine how many heavy chains were required for ceruloplasmin to interact with ferritin such that iron loading occurred. The cDNA sequences encoding the heavy and light chains of rat liver ferritin were cloned into the baculovirus transfer vector pA-cUW51 under the control of polyhedrin and p10 promoters, respectively, which was then incorporated by homologous recombination into the infections Autographa californica nuclear polyhedrosis virus genome. Both ferritin chains were expressed and assembled into two heteropolymers following the infection of insect cells by recombinant virus, which were separated by DEAE-Sepharose chromatography. The percentage of heavy (H) and light (L) chains making up the two heteropolymers, determined by gel scanning following the resolution of chains on SDS-PAGE, were equivalent to 1 H and 23 L chains and 2 H and 22 L chains. The maximal extent of iron loading was observed using 1 mol of rat ceruloplasmin per mole of H chain in the two heteropolymers. The extent of iron incorporation decreased with additional ceruloplasmin. Iron incorporation into rat liver ferritin, found to contain 10 H chains, increased as the molar ratio of ceruloplasmin to ferritin increased to 4:1 and remained the same up to 8:1. Iron loading into horse spleen ferritin, found to have one H chain, appeared similar to that for recombinant ferritin, having only one H chain. Therefore, we propose that the optimal molar ratio of ceruloplasmin to ferritin depends upon the numbers of H chain making up the ferritin molecule for the maximal incorporation of iron into ferritin. These results also suggest that the iron loading channel is contained within a single H chain subunit.
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PMID:Loading of iron into recombinant rat liver ferritin heteropolymers by ceruloplasmin. 916 16

In order to improve the non aggressive diagnosis of hepatic metastasis from digestive neoplasm, the authors analyzed the following biological parameters: aminotransferases, alkaline phosphatase and lacticodehydrogenase isoenzymes, gammaglutamyl-transpeptidase, conjugated and total bilirubin, C-reactive protein, type A, G, M immunoglobulins, C3 complement factor, alpha-1 acidic glycoprotein (orosomucoid), haptoglobin, ceruloplasmin, transferrin, albumin, prealbumin, ferritin. This work included 54 patients with digestive tract cancer (esophageal, gastric, colic, rectal, anal localizations), divided in two groups: M- (n = 27), without hepatic metastasis), and M+ (n = 27, with histological confirmed hepatic metastasis). The Mann-Whitney test showed significant differences for 12 parameters between the 2 groups. With more than 60% sensitivity (Se) and specificity (Sp), according to the ROC curves, the following parameters can be selected: Total alkaline phosphatase (Se 89%, Sp 70%) and their macromolecular H2 fraction, lacticodehydrogenase fraction 4 (Se 63%, Sp 63%), gammaglutamyl-transpeptidase (Se 85%, Sp 82%), ceruloplasmin (Se 64%, Sp 65%), aspartate-aminotransferase determination (Se 63%, Sp 65%).
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PMID:[Detection of liver metastases from digestive cancer. Value of alkaline phosphatases, their macromolecular isoenzyme and of ceruloplasmin]. 923 22

There is increasing experimental evidence that oxidation of LDL plays a major role in the pathogenesis of coronary artery disease (CAD). However, results from clinical studies on LDL oxidation and CAD are not consistent. In most studies only single plasma factors of LDL oxidation have been determined. We studied 207 patients who underwent coronary angiography. They were divided into subjects with CAD (n = 137) and those without CAD (n = 70). We determined the susceptibility of LDL to in vitro oxidation (lag phase), potential prooxidative and antioxidative plasma factors (plasma vitamin E, LDL vitamin E, ascorbate, iron, copper, ferritin, and ceruloplasmin), and markers of in vivo LDL oxidation (autoantibodies to malondialdehyde-modified LDL, oxidized LDL, and thiobarbituric acid-reactive substances), plasma lipids and lipoproteins, smoking habits, and other coronary risk factors in both groups. The lag phase was significantly shorter in patients with CAD than in patients without CAD (101 +/- 38.6 versus 119 +/- 40.6 minutes, P < .01). There was no correlation between the lag phase and the other oxidation parameters or the coronary risk factors. In multivariate regression analyses the lag phase remained significant in all tested models. Our data suggest that a short lag phase of LDL oxidation might be an independent risk factor of CAD.
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PMID:Increased oxidation of LDL in patients with coronary artery disease is independent from dietary vitamins E and C. 926 Dec 77

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.
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PMID:Stimulation of the ferroxidase activity of ceruloplasmin during iron loading into ferritin. 936 31

A 56-year-old Japanese man was diagnosed as having hereditary ceruloplasmin deficiency. His ceruloplasmin concentration was below the lower limit of detection. Serum copper and iron concentrations were below normal, but the ferritin concentration was highly elevated. An ophthalmoscopic examination showed retinal degeneration with yellowish discoloration of the fundus in both eyes. Fluorescein angiography demonstrated a dark choroid in the posterior pole. Geographic areas of window defects were seen in the midperipheral fundus. The retinal degeneration in this patient was thought to be caused by the cellular iron deposition that occurred as a result of ceruloplasmin deficiency.
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PMID:Retinal degeneration in hereditary ceruloplasmin deficiency. 943 77

The L chain of the iron storage protein ferritin contains more putative nucleation sites in the core (Glu53, 56, 57, 60, and 63) than does the H chain (Glu61, 64, and 67). Recombinant DNA techniques were used to investigate the role of these putative nucleation sites on iron loading by ceruloplasmin and on the stability of the iron core. Recombinant rat liver ferritin H chain homopolymer and the two mutants (E61A and E61A-E64A), containing three, two and one nucleation sites, respectively, loaded up to 2010 +/- 50, 2010 +/- 40, and 1950 +/- 40 atoms of iron per ferritin, respectively. However, the mutations resulted in a 50% decrease in the rate of iron loading by ceruloplasmin. The ferritin variants incorporated the same amount of phosphate after iron loading (410 +/- 20, 400 +/- 30, and 420 +/- 20 atoms per ferritin, respectively). The stability of the iron cores prior to phosphate incorporation, assessed by the rate of iron release by 10 mM EDTA and the paraquat cation radical, corresponded to numbers of proposed nucleation sites. The subsequent incorporation of phosphate seemed to stabilize the iron core and minimized the effect of numbers of putative nucleation sites in ferritin on the rate of iron release by EDTA and the paraquat cation radical. After incorporation of phosphate the ferritins behaved similarly to the native rat liver ferritin with respect to the rate of iron release by the paraquat cation radical.
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PMID:The effect of putative nucleation sites on the loading and stability of iron in ferritin. 947

We previously reported that the heavy chain of ferritin was required for loading it with iron using ceruloplasmin as a ferroxidase [J.-H. Guo, M. Abedi, and S. D. Aust (1996) Arch. Biochem. Biophys. 335, 197-204]. Site-directed mutagenesis, K58E and G61H, on recombinant rat liver L chain ferritin (rL-Ft) was performed to construct a proposed iron-loading channel in the alpha-helix bundle similar to rat liver H chain ferritin (rH-Ft). Conversely, the channel in rH-Ft was closed by mutations E62K and H65G to form a K62 to E107 salt bridge, which is believed to exist in the L chain. Both variants were expressed in insect cells and were soluble and able to form multi-subunit homopolymers. The rH-Ft mutant homopolymer could not be loaded, whereas the rL-Ft mutant homopolymer could be loaded with iron by ceruloplasmin. However, we found that the initial rate of iron loading into the rL-Ft mutant homopolymer by ceruloplasmin was less than that into the rH-Ft homopolymer. When 500 atoms of iron per ferritin were used for loading, 98% was loaded into the rH-Ft homopolymer by ceruloplasmin in 15 min, but only 30% was loaded into the rL-Ft mutant homopolymer in the same time. Moreover, the ferroxidase activity of ceruloplasmin was enhanced in the presence of the rH-Ft and the rH-Ft mutant homopolymers, but not in the presence of the rL-Ft or the rL-Ft mutant homopolymers. These observations suggested that the four alpha-helix bundle channel of ferritin is required for iron loading, but an additional factor, i.e. , a site which stimulate the ferroxidase activity of ceruloplasmin, is also essential.
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PMID:Mutational analysis of the four alpha-helix bundle iron-loading channel of rat liver ferritin. 952 17

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.
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PMID:A novel splicing mutation in the ceruloplasmin gene responsible for hereditary ceruloplasmin deficiency with hemosiderosis. 955 83

The formation of a protein-protein complex for the loading of iron into ferritin by ceruloplasmin was investigated. Ferritin stimulated the ferroxidase activity of ceruloplasmin unless the ferritin was fully loaded, in which case it inhibited the ferroxidase activity of ceruloplasmin. The apparent association constant for the interaction of ferritin and ceruloplasmin was 24 nM. Isothermal titration calorimetry indicated that the interaction of ceruloplasmin and ferritin was endothermic, driven by positive changes in entropy. The association constants for complex formation between ferritin and ceruloplasmin were 4.5 +/- 0.7 x 10(5) and 9.5 +/- 0.3 x 10(4) M-1 for the reduced and oxidized forms of ceruloplasmin, respectively. The oxidized form of ceruloplasmin was retained on an affinity column with ferritin immobilized as the ligand and remained bound to the column with mobile phases of increased hydrophobicity, but was eluted with increased ionic strength. The ability of ceruloplasmin to remain bound to the affinity resin was affected by the species from which ceruloplasmin was isolated. Gradient ultracentrifugation also provided evidence that the two proteins were associated, since ferritin promoted migration of ceruloplasmin through the gradient. Including ferrous iron in the gradient resulted in reduction of ceruloplasmin and increased the mobility of ceruloplasmin with ferritin. These data provide evidence that ferritin and ceruloplasmin form a protein-protein complex during iron loading into ferritin, which may limit redox cycling of iron in vivo.
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PMID:Evidence for a protein-protein complex during iron loading into ferritin by ceruloplasmin. 963 12

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.
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PMID:Studies on the interaction between ferritin and ceruloplasmin. 964 67


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