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)

Cyanosis, clubbing, and arterial oxygen desaturation may occur in patients with liver disease, and are attributed to the presence of pulmonary or peripheral arterio-venous shunting. Cardiac catheterisation and angiocardiography in a patient with a normal heart did not demonstrate the presence of abnormal arterio-venous anastomoses. Pulmonary shunting was proved when intravenous technetium-labelled macroaggregated albumin, normally held up in capillary networks, was passed quickly through the lungs and immediately detected in high systemic blood flow organs. The opening of peripheral and pulmonary anastomoses in patients with liver disease may be owing to the presence of a vasodilatory substance such as ferritin, which was found to be abnormally increased in the patient's blood.
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PMID:Pulmonary arterio-venous fistulae in hepatic cirrhosis. 622 1

During inflammation, the superoxide anion (O-2) and hydrogen peroxide (H2O2) are produced by stimulated polymorphonuclear leukocytes and macrophages. The toxic effects of these reactive oxygen intermediates increase when traces of iron are present, because iron catalyzes the formation of the hydroxyl radical (OH.). Partially saturated iron-binding proteins, such as transferrin and ferritin, are unable to catalyze OH. formation in vitro. Mobilization of iron from these proteins is necessary for iron stimulation of OH. formation. This paper reports that stimulated polymorphonuclear leukocytes mobilize iron from human and horse ferritin, but not from human transferrin. Iron release from ferritin depends on O-2 because it can be prevented by the addition of superoxide dismutase. Catalase and dimethylsulfoxide have no inhibitory effect on iron mobilization. The efficiency of the iron release increases at low levels of O-2 production. Only O-2 produced by granulocytes is sufficient for iron mobilization, because solid potassium superoxide is also able to release iron from ferritin. We propose that this reaction may potentiate the formation of the OH. radical in inflammatory states.
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PMID:Iron mobilization from ferritin by superoxide derived from stimulated polymorphonuclear leukocytes. Possible mechanism in inflammation diseases. 632 64

Superoxide anion production in resting and PMA- or zymosan-stimulated neutrophils was evaluated in 21 beta-thalassemia patients. The results were correlated with ferritin values, hepatitis B virus serum markers, liver pathology, immunoglobulin levels and T-cell subsets. Superoxide anion generation from resting or PMA-stimulated neutrophils was significantly higher in patients than in controls. On the contrary, zymosan-stimulated neutrophils showed reduced superoxide anion production. Increased superoxide anion production in resting neutrophils showed a significant correlation to the values of ferritin. In addition, patients with biopsy-proven chronic liver disease showed significantly increased ferritin levels and superoxide anion production as compared to the remaining patients. No correlation was observed between superoxide anion production and the presence or the absence of hepatitis B virus serum markers, immunoglobulin levels and T-cell subsets. A possible role of interreactions between iron and oxygen radicals in determining liver damage in beta-thalassemia patients is suggested.
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PMID:Changes in superoxide anion production in neutrophils from multitransfused beta-thalassemia patients: correlation with ferritin levels and liver damage. 633 Oct 44

Nonheme iron is synergistic with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in producing hepatotoxicity in mice. Fe2+ rather than Fe3+ is the probable toxin and we speculated that TCDD, an inducer of microsomal electron transport, might favour reduction of iron. We have defined a system which will release Fe2+ from ferritin (Fe3+) under anaerobic conditions and in the presence of added flavin mononucleotide (FMN). The rate of reduction iron was proportional (a) to microsomal protein from 0.5 to greater than 3 mg/mL, (b) to the activity of NADPH-cytochrome c reductase over 0.1 U/mL, (c) to ferritin at concentrations exceeding iron concentrations greater than 200 mumol/L, and (d) to the concentration of FMN when it was less than 125 mumol/L. The system was approximately twice as active with NADPH as with NADH as electron donor. The linear phase of iron release did not commence immediately, but followed a delay (+/- 0.5 min) after adding FMN to an anaerobic mixture containing microsomes, ferritin, an NADPH-generating system, and an oxygen-scavenging system. When microsomes from untreated, phenobarbital-treated (3 days), or TCDD-treated (1 or 3 weeks) rats were compared, iron release correlated most closely with the cytochrome P-450 concentration. However, when the microsomal proteins were solubilized and the NADPH-cytochrome c reductase and cytochrome P-450 activities were separated, reduction of ferritin iron was shown to be a function only of the reductase fraction, except that the delay in initiating release of Fe2+ was increased with purified reductase and decreased when a monooxygenase system was reconstituted with cytochrome (phenobarbital or TCDD induced) and lipid.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Release of ferrous iron from ferritin by liver microsomes: a possible role in the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin. 644 9

Serum erythropoietin (EPO) was measured in 64 children with chronic renal failure (CRF) by means of the fetal mouse liver cell assay. The results were compared with two control groups consisting of 20 healthy children and 10 with nonrenal anemia. EPO was analyzed according to the mode of treatment and the degree of uremia, anemia, hypoxemia, hyperparathyroidism, and body iron load. Mean EPO was 36 U/liter on conservative treatment (CT) (N = 30), similar to that in healthy children (35 U/liter) and in 15 children with renal transplants (TP, 39 U/liter), but significantly higher than that in 19 patients on regular dialysis (RDT; 16 U/liter) and lower than that in children with nonrenal anemia but with similar hemoglobin (230 U/liter). On CT, EPO was higher with severe uremia (SCr greater than 4 mg/dl) compared with moderate CRF and was inversely correlated with hemoglobin, but on a lower level compared with control, whereas on RDT the correlation became positive. By serial measurements, the decrease of EPO from CT to RDT was confirmed. An inverse relationship between EPO and p50 or the oxygen transport index was detected only on CT and after TP. EPO was inversely correlated with serum ferritin levels on HD. Between EPO and PTH, no correlation was found. Data demonstrate a negative feedback between EPO and the degree of hypoxia in children with CRF. On CT, this regulatory mechanism of erythropoiesis is acting on a lower level than it does in control subjects and is lost on RDT.
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PMID:Serum erythropoietin levels in children with chronic renal failure. 658 79

Control of ferritin synthesis by iron at the level of transcription is potentially hazardous to DNA because of the iron-catalyzed degradation of DNA. The induction of ferritin synthesis in reticulocytes of embryos (bullfrog tadpoles) occurs by two types of translational control i.e. increased availability of stored ferritin mRNA, in response to iron, coupled with a high translational efficiency. Since erythroid cell nuclei have large amounts of heterochromatin and may be relatively inactive genetically, the translational control of ferritin by iron observed in red cells was studied in other tissue by isolating poly (A+) RNA from tadpole liver and analyzing protein synthesis in vitro. Liver ferritin mRNA directed the synthesis of 7.0% of the protein in a wheat germ system, compared to 1.2% in vivo, suggesting that tadpole liver contained a large amount of stored ferritin mRNA. At levels of poly (A+) RNA which were saturating for total protein synthesis, ferritin synthesis was still linearly dependent upon RNA concentration, indicating a high efficiency of translation of ferritin mRNA. The results are analogous to those previously observed in red cells and confirm the storage of ferritin mRNA deduced from studies of the polysomal and nonpolysomal distribution of the mRNA in rat liver. The results indicate that the increased availability for translation of stored ferritin mRNA, in response to iron, and the high translational efficiency of ferritin mRNA are a general characteristic of ferritin synthesis rather than a specific feature of red cell maturation. This novel form of regulation of ferritin gene expression can be attributed to a need to protect DNA from degradation by iron and oxygen. The normal barrier between DNA and iron is apparently breached by the iron-oxygen complex of the drug bleomycin, an antitumor agent thought to act in vivo by iron-catalyzed cleavage of DNA.
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PMID:Regulation of ferritin mRNA: a possible gene-sparing phenomenon. Induction of ferritin synthesis by iron in liver as well as red cells combines high translational efficiency with increased utilization of preformed ferritin mRNA. 660 2

We investigated 28 cystic fibrosis (CF) patients to determine why hypoxia from their obstructive pulmonary disease does not produce polycythemia. Oxygen saturation was lower and erythropoietin levels were higher in CF patients than in 25 age-comparable reference subjects (90.8% and 47 mimu vs. 94.7% and 29 mimu, p less than 0.01). Hematocrit and red blood cell (RBC) indices were not different between groups. Serum vitamin and iron levels, ferrokinetics, RBC volume, and RBC survival were studied in 10 of the 28 CF patients. Total iron-binding capacity and vitamin E levels were low, and serum iron, ferritin, vitamin B12, and folate levels were normal in these patients. Red blood cell survival was minimally decreased in six patients although there was no other evidence for hemolysis. Ferrokinetics (59Fe) indicated a reduction in total erythropoiesis in only two patients. Plasma volume was high-normal in five and above normal in four CF patients; RBC mass was increased appropriately for each patient's degree of hypoxia, when compared to healthy individuals living at different altitudes. These results suggest that CF patients are able to compensate for hypoxia by increasing RBC mass; however, an expanded plasma volume prevents a detectable rise in hematocrit.
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PMID:Ferrokinetic and hematologic studies in cystic fibrosis patients. 661 95

A STEM VG HB 501 equipped with a Gatan spectrometer has been interfaced to a PDP 11-34 computer. Digital energy filtered images have been recorded with several energy windows on both sides of a characteristic level, so that the exact background can be stripped under the core loss signal for each pixel. Results concern the distribution of nitrogen (K-edge at 402 eV), oxygen (K-edge at 532 eV) and iron (L23 edge at 705 eV) in embedded sections of bone marrow. The present performances of the system allow the detection of composition variations of 1 to 2% for these elements, with a lateral accuracy of the order of 5 nm in a section of 50 nm thickness. Individual ferritin molecules distributed within the section are clearly imaged and analyzed with the characteristic iron edge.
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PMID:Electron energy loss chemical mapping of low Z elements in biological sections. 663 71

Cell-specific variations in apoferritin structure correlate with variations in iron metabolism that suggest functional specificity of the protein shell. Using EPR spectroscopy, we previously showed that vanadyl binds to specific sites on apoferritin, and that VO2+ binding is reduced by Fe(II) and Fe(III) (the natural substrates) and by metals known to influence iron storage (Chasteen, N. D., and Theil, E. C. (1982) J. Biol. Chem. 257, 7672-7677). Such observations suggest that the metal-binding site is important to apoferritin function and may define a location where the influence of cell-specific structural features are exerted. To investigate the iron-protein complex further, we have used x-ray absorption spectroscopy and have characterized, for the first time to our knowledge, Fe(III) apparently attached to the protein, after analyzing the x-ray absorption spectrum of an Fe(III)-apoferritin complex (10 Fe/molecule) compared to that of ferritin (polynuclear Fe(III)OOH, about 2000/molecule). The environment of iron in the Fe(III)-protein complex was similar to that in an Fe(III)-oxalate (2:3) hexahydrate complex, both in near edge structure and extended x-ray absorption structure, confirming earlier predictions of carboxylates as protein ligands. The extended x-ray absorption fine structure data for both compounds was fit best by a model in which a second shell of low Z atoms (carbon) was close (0.53-0.55 A) to the first shell of coordinated oxygen. However, small differences between Fe(III)-apoferritin and Fe(III)-oxalate in the Fe-O environment suggest a distorted geometry in the Fe(III)-protein complex and/or the presence of a mixture of atoms, such as nitrogen and oxygen, coordinated to iron. Extension of this approach to other apoferritins and metals will be likely to clarify the role of cell-specific features of the apoprotein in the formation of the iron core.
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PMID:A distinct environment for iron (III) in the complex with horse spleen apoferritin observed by x-ray absorption spectroscopy. 664 67

In a patient with sickle cell anemia, iron deficiency was accompanied by hypochromic, microcytic RBCs, absence of bone marrow iron, and a low serum ferritin level. The mean corpuscular hemoglobin concentration (MCHC) was decreased (27.6 g/dL) and was associated with an extreme scarcity of sickled erythrocytes in blood smears. Iron therapy resulted in reticulocytosis and an increase in sickled erythrocytes. In vitro studies demonstrated a decrease in sickling of erythrocytes as a function of oxygen saturation of the blood when the patient was iron deficient. The whole blood oxygen dissociation curve showed a substantial decrease in oxygen pressure necessary to produce 50% saturation of hemoglobin at pH 7.4 and 37 degrees C (P50), indicating an increased oxygen affinity. These data suggest that a reduction of the MCHC induced by iron deficiency may ameliorate sickling.
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PMID:Iron deficiency and sickle cell anemia. 667 16


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