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)

Low density lipoprotein (LDL) oxidation mediated by phorbol myristate acetate (PMA)- and formylmethionylleucylphenylalanine (FMLP) -stimulated human neutrophils was enhanced by 70% in the presence of ferritin. Iron released from ferritin by the superoxide anion generated in the respiratory burst of stimulated neutrophils is shown to be involved in lipoprotein oxidation. Ascorbate (100 microM), superoxide dismutase (10 micrograms/ml) and uric acid (430 microM) showed inhibitory effects of 30% [corrected], 70% and 50% on LDL oxidation, respectively. Ceruloplasmin (2.7 microM) potentiated LDL oxidation by stimulated neutrophils and ferritin, both alone and in the presence of methionine. Methionine (1 mM) and catalase (30 micrograms/ml) increased LDL oxidation by stimulated neutrophils and ferritin. These data suggest that LDL oxidation by stimulated neutrophils and ferritin may be relevant in inflammation when both neutrophils and ferritin are increased.
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PMID:Low density lipoprotein oxidation by stimulated neutrophils and ferritin. 133 54

Ceruloplasmin catalyzed the incorporation of iron into apoferritin with a stoichiometry of 3.8 Fe(II)/O2. This value remained the same when ferritin containing varying amounts of iron was used. Contrary to the "crystal growth" model for ferritin formation, no iron incorporation into holoferritin was observed in the absence of ceruloplasmin. Fe(II)/O2 ratios close to 2 were obtained for iron incorporation into apo- and holoferritin in Hepes buffer, in the absence of ceruloplasmin, indicating the formation of reduced oxygen species. Sequential loading of ferritin in this buffer resulted in increasing oxidation of the protein as measured by carbonyl formation. Sequential loading of ferritin using ceruloplasmin did not result in protein oxidation and a maximum of about 2300 atoms of iron were incorporated into rat liver ferritin. This corresponded to the maximum amount of iron found in rat liver ferritin in vivo after injection with iron. These results provide evidence for ceruloplasmin as an effective catalyst for the incorporation of iron into both apo- and holoferritin. The possibility that these findings may have physiological significance is discussed.
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PMID:Stoichiometry of Fe(II) oxidation during ceruloplasmin-catalyzed loading of ferritin. 152 35

Ceruloplasmin (CP) effectively inhibited superoxide and ferritin-dependent peroxidation of phospholipid liposomes, using xanthine oxidase or gamma irradiation of water as sources of superoxide. In addition, CP inhibited superoxide-dependent mobilization of iron from ferritin, suggesting that CP inhibited lipid peroxidation by decreasing the availability of iron from ferritin. CP also exhibited some superoxide scavenging activity as evidenced by its inhibition of superoxide-dependent cytochrome c reduction. However, superoxide scavenging by CP did not quantitatively account for its inhibitory effects on iron release. The effects of CP on iron-catalyzed lipid peroxidation in systems containing exogenously added ferrous iron was also investigated. CP exhibited prooxidant and antioxidant effects; CP stimulated at lower concentrations, reached a maximum, and inhibited at higher concentrations. However, the addition of apoferritin inhibited CP and Fe(II)-catalyzed lipid peroxidation at all concentrations of CP. In addition, CP catalyzed the incorporation of Fe(II) into apoferritin. Collectively these data suggest that CP inhibits superoxide and ferritin-dependent lipid peroxidation via its ability to incorporate reductively-mobilized iron into ferritin.
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PMID:Effects of ceruloplasmin on superoxide-dependent iron release from ferritin and lipid peroxidation. 164 82

Transferrin receptors were characterized with 125I-ferrotransferrin on membrane fractions prepared from the rodent forebrain. The distribution of transferrin receptors in the rat brain was investigated further by in vitro autoradiography. Saturation binding analysis revealed an apparent single class of sites with a dissociation constant of 2 nM and a binding site density of 15 pmol/g. The Hill coefficient derived from these data was 1.05, indicating the absence of cooperativity and that 125I-ferrotransferrin binds to a single class of sites. Estimates of the kinetically determined KD for forebrain membranes were within the 2-4 nM range, in agreement with the equilibrium measurements. Apotransferrin and ferrotransferrin competitively displaced the binding of 125I-ferrotransferrin, while ferritin, albumin, and cytochrome c failed to compete for the binding site. Ceruloplasmin, the copper transport protein, was a weak inhibitor of 125I-ferrotransferrin binding. Autoradiographic localization studies demonstrate a heterogeneous distribution of transferrin receptors in the rat brain. Transferrin receptor densities were markedly elevated over the cerebral cortex and the hippocampus. Moderate to high 125I-ferrotransferrin binding was also apparent throughout areas involved in motor functions, including the caudate-putamen, the nucleus accumbens, the substantia nigra, the red nucleus, and the cerebellum.
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PMID:Characterization and distribution of transferrin receptors in the rat brain. 223 Aug 4

Ceruloplasmin (CP) was found to inhibit xanthine oxidase and ferritin-dependent peroxidation of phospholipid liposomes, as evidenced by decreased malondialdehyde formation. Ceruloplasmin was also shown to inhibit superoxide-mediated mobilization of iron from ferritin, in a concentration-dependent manner, as measured spectrophotometrically using the iron(II) chelator bathophenanthroline sulfonate. Ceruloplasmin failed to function as a peroxyl radical-scavenging antioxidant as evidenced by its inability to inhibit free radical-initiated peroxidation of linoleic acid, suggesting that CP inhibited lipid peroxidation by affecting the availability of ferritin-derived iron. In addition, CP scavenged xanthine oxidase-derived superoxide as measured spectrophotometrically via its effect on cytochrome c reduction. However, the extent of the superoxide scavenging of CP did not quantitatively account for its effects on iron release, suggesting that CP inhibits superoxide-dependent mobilization of ferritin iron independently of its ability to scavenge superoxide. The effects of CP and apoferritin on iron-catalyzed lipid peroxidation in systems containing exogenously added ferrous iron was also investigated. In the absence of apoferritin, CP exhibited a concentration-dependent prooxidant effect. However, CP-dependent, iron-catalyzed lipid peroxidation was inhibited by the addition of apoferritin. Apoferritin did not function as a peroxyl radical-scavenging antioxidant but was shown to incorporate iron in the presence of CP. These data suggest that CP inhibits superoxide and ferritin-dependent lipid peroxidation largely via its ability to reincorporate reductively mobilized iron back into ferritin.
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PMID:Inhibition of superoxide and ferritin-dependent lipid peroxidation by ceruloplasmin. 253 39

Ceruloplasmin, a copper ferroxidase, promotes the incorporation of Fe(III) into the iron storage protein, apoferritin. The product formed is identical to ferritin as judged by polyacrylamide electrophoresis and iron/protein measurements. Of several proteins examined, only apoferritin accumulates the Fe(III) produced by ceruloplasmin. When ceruloplasmin was replaced by tyrosinase, which we have shown to have ferroxidase activity, no iron incorporation into apoferritin was observed. It is proposed that Fe(III) is transferred directly and specifically to apoferritin. These data support a more specific role for ceruloplasmin in iron metabolism than has previously been proposed.
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PMID:The incorporation of iron into apoferritin as mediated by ceruloplasmin. 641 53

Oxygen free radicals are probably involved in the pathogenesis of rheumatoid arthritis (RA). The enzymes involved in protection against oxygen free radicals and H2O2 (superoxide dismutase, catalase, and glutathione peroxidase) were measured. Superoxide dismutase was not increased, glutathione peroxidase was slightly and catalase was strongly elevated in RA synovial fluid (SF) compared with control SF. Although these enzymes are present in SF, the activities are insufficient to protect against oxygen free radicals and H2O2. In contrast to transferrin, ferritin was increased in RA synovial fluid. Ceruloplasmin was also elevated. When rat liver microsomes were used as a target for oxygen free radicals, serum and SF were both protective. Gel filtration experiments showed that the fraction pattern in which there was maximal protective potential against lipid peroxidation corresponded closely to the level of ceruloplasmin. After removal of ceruloplasmin from serum or SF, about 70% of the protective capacity disappeared. It is concluded that ceruloplasmin is an important protector against oxygen free radicals.
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PMID:Protective factors against oxygen free radicals and hydrogen peroxide in rheumatoid arthritis synovial fluid. 674 61

Iron and copper catalyze lipid peroxidation in vitro, and recent epidemiological data suggest that these metal ions might also be involved in human coronary heart disease. We tested the hypothesis by investigating whether the storage proteins ferritin and ceruloplasmin were coronary risk factors. A nested case-control study was set up in middle-aged dyslipidaemic participants of the Helsinki Heart Study: a placebo-controlled coronary primary prevention trial with gemfibrozil. Of the 140 subjects with cardiac end-points (non-fatal myocardial infarction or cardiac death) 136 were matched with controls for geographical area and drug treatment (gemfibrozil-placebo). Frozen baseline serum samples were used in the analyses of ferritin and ceruloplasmin. Using logistic regression analyses no increment in coronary risk was detected with increasing ferritin levels (P = 0.8 for trend). Ceruloplasmin was higher 349 +/- 86 vs 317 +/- 77 mg.l-1 (P < 0.001) in cases than in controls and the risk in the highest tertile was two-fold (odds ratio 2.1; 95% CI 1.1-4.2) compared to the lowest (P < 0.005 for trend). The risk of high ceruloplasmin was influenced by lipoprotein cholesterol concentrations, with an odds ratio of 2.4 (95% CI 1.3-4.4) in subjects with high low density lipoprotein cholesterol and of 11.3 (95% CI 2.5-52.2) in subjects with low high density lipoprotein cholesterol. It was concluded that ferritin was not associated with coronary heart disease in dyslipidaemic, middle-aged men, while there was a continuous and graded increment in coronary risk with elevating ceruloplasmin level.
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PMID:Serum ferritin and ceruloplasmin as coronary risk factors. 769 27

When erythrocyte membranes were incubated with adriamycin (ADM) in the presence of ferritin, lipid peroxidation occurred with release of iron from the ferritin. In the presence of apoferritin, ADM did not cause lipid peroxidation. Deferoxamine inhibited the ADM-induced lipid peroxidation in the presence of ferritin. These results indicate that lipid peroxidation depends upon the release of iron from ferritin. Even when the iron content in ferritin was very low, ADM could induce lipid peroxidation. Superoxide dismutase, catalase and hydroxyl radical scavengers did not substantially affect lipid peroxidation, indicating that the peroxidation reaction was independent of superoxide, H2O2 and hydroxyl radicals. Ceruloplasmin, a ferroxidase, markedly inhibited lipid peroxidation but did not affect the release of iron from ferritin. ADM-Fe(3+)-binding erythrocyte membranes were readily formed during the incubation of erythrocyte membranes with ADM in the presence of ferritin, and deferoxamine removed iron from the ADM-Fe(3+)-binding membranes, indicating that the iron moiety of the ADM-Fe(3+) complex is exposed at the membrane surface. These results may suggest that the peroxidation reaction occurs in a site-specific manner.
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PMID:Adriamycin-induced lipid peroxidation of erythrocyte membranes in the presence of ferritin and the inhibitory effect of ceruloplasmin. 840 98

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


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