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)

A systematic analysis of the blast cell population was carried out on samples from 50 patients suffering from blast transformation of chronic granulocytic leukaemia (CGL) (31) and of myelofibrosis (4), acute myelofibrosis (AM) (11) and undifferentiated acute leukaemia (4). Transmission electron microscopy (TEM), used in 41 samples, included: morphology and techniques for myeloperoxidase (MPO), platelet-peroxidase (PPO) and acid phosphatase (AP). The majority of cases were also studied by light microscopy cytochemistry and with a battery of cell markers which are reported in the accompanying paper (San Miguel et al, 1985). The characterization of the type(s) of proliferating blasts was made from the integration of ultrastructural and immunological data. TEM morphology allowed the precise recognition of specific granules in basophil and mast-cell precursors and of ferritin particles in blasts of erythroid lineage; these rare cell types were not adequately characterized by other methods. The PPO reaction made possible the identification of pure megakaryoblastic proliferations in 38% of cases, including eight of the 11 with AM; megakaryoblasts were also present in nine of 12 cases with mixed blast cell types. The MPO and AP reactions were useful for the characterization of myeloblasts and monoblasts, respectively. Lymphoblasts could be distinguished from other cell types by TEM morphology and negative MPO and PPO reactions. TEM techniques were valuable for diagnosing correctly the type of blast cell in this study in which only four cases (8%) remained unclassifiable.
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PMID:Characterization of blast cells in chronic granulocytic leukaemia in transformation, acute myelofibrosis and undifferentiated leukaemia. I. Ultrastructural morphology and cytochemistry. 385 50

Intracellular ferritin in newt (Triturus cristatus) erythroblasts was accessible to the chelating effects of EDTA and pyridoxal phosphate. EDTA (0.5-1 mM) promoted release of radioactive iron from ferritin of pulse-labelled erythroblasts during chase incubation, but its continuous presence was not necessary for ferritin iron mobilization. Brief exposure to EDTA was sufficient to release 60-70% of ferritin 59Fe content during ensuing chase in EDTA-free medium. EDTA also suppressed cellular iron uptake and utilization for heme synthesis, but these activities were restored upon its removal. Pyridoxal-5'-phosphate (0.5-5 mM) also stimulated loss of radioactive iron from ferritin; however, ferritin iron release by pyridoxal phosphate required its continued presence. Unlike EDTA, pyridoxal phosphate did not interfere with iron uptake or its utilization for heme synthesis. Chelator-mobilized ferritin iron accumulated initially in the hemolysate as a low-molecular-weight component and appeared to be eventually released into the medium. No radioactive ferritin was found in the medium of chelator-treated cells, indicating that secretion or loss of ferritin was not responsible for decreasing cellular ferritin 59Fe content. Moreover, there was no transfer of radioactive iron between the low-molecular-weight component released into the medium and plasma transferrin. These results indicate that chelator-released ferritin iron is not available for cellular utilization in heme synthesis and that ferritin iron released by this process is not an alternative or complementary iron source for heme synthesis. Correlation of these data with effects of succinylacetone inhibition of heme synthesis and with previous studies indicates that the main role of erythroid cell ferritin is absorption and storage of excess iron not used for heme synthesis.
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PMID:Mobilization of ferritin iron in erythroblasts by chelating agents. 391 75

The regulation of transferrin and iron release from the liver was studied using adult rat hepatocytes in primary monolayer culture. The cells were prelabeled by incubation with rat transferrin doubly labeled with iodine-125 and iron-59. Approximately 50% of the 125I-transferrin but only 10% of the iron-59 taken up by the cells was released during reincubation for 24 h. Less than 10% of the refluxed transferrin was catabolized as indicated by the protein-free iodine-125 values. These results suggest that at least part of iron uptake by hepatocytes is mediated by the reversible binding of transferrin in a manner comparable with erythroid cells and placenta. However, several iron chelators mobilized hepatic iron, in contrast to erythroid cells. Apotransferrin and desferrioxamine released a maximum of about 20% iron-59 with little effect on transferrin binding. A greater proportion of the iron-59 was available for chelation after shorter uptake times (1-2 h) than longer times. Hence, there are at least three iron compartments in hepatocytes in culture: rapidly refluxing iron that may be transferrin bound, a fixed pool, and a chelatable pool that may represent iron in transit between plasma transferrin and ferritin.
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PMID:Transferrin and iron release from rat hepatocytes in culture. 396 65

Normal human erythroid progenitor cells from bone marrow were grown in culture using a methyl cellulose clonal assay technique. Sideroblastic erythroid cells were found in the majority of colonies examined at 14-17 days, and a few sideroblasts were found in some of the colonies examined after shorter periods of culture. Electron microscopy confirmed the presence of both intramitochondrial iron deposits and cytoplasmic ferritin aggregates. These morphological appearances probably represent an abnormality induced by the in vitro culture conditions and cannot be used as evidence for an intrinsic defect in haem synthesis.
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PMID:Sideroblastic colonies in erythroid cultures grown from normal human marrow. 396 11

21-day-old female Norwegian Hooded rats were fed a riboflavin-deficient diet for 7 weeks. A control group consisted of individually weight-matched rats fed a complete diet. Reticulocytosis was induced by phlebotomy and heme synthesis measured in a reticulocyte-rich preparation in vitro. Concentrations of circulating iron and liver stores of ferritin iron and non-heme iron were measured. Riboflavin deficiency significantly impaired the process of accumulation and maintenance of hepatic iron stores but did not appear to influence the rate of heme synthesis in an in vitro system. A primary lesion in iron metabolism in young riboflavin-deficient rats may be at the level of iron absorption so that assimilated iron is diverted to the erythroid marrow at the expense of repleting iron stores.
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PMID:Experiment to determine the effect of riboflavin deficiency at weaning on iron economy and heme synthesis. 405 48

Simultaneous detection of specific surface markers by immunogold and intracellular peroxidase activity was determined ultrastructurally in normal and leukaemic progenitors of platelets, erythrocytes and granulocytes. A new method of fixation was employed to preserve platelet peroxidase activity. Monoclonal antibodies to platelet glycoproteins labelled exclusively platelet peroxidase (PPO) positive cells, i.e. platelets, megakaryocytes and promegakaryoblasts (PMKB). In acute megakaryoblastic leukaemia, most PMKB possessed both markers while a few PMKB identified by PPO did not bind monoclonal antibodies. This result suggests that PPO appears earlier in maturation than platelet glycoproteins. Although all glycoproteins (GP) displayed fewer sites in PMKB than platelets, GP Ib was often observed in more mature megakaryocytes. Surface (glycophorin A) and intracytoplasmic markers including ferritin, intra-mitrochondrial iron and diffuse peroxidase activity due to haemoglobin of erythroid progenitors, appeared simultaneously. The number of glycophorin A sites increased with maturation. In leukaemia involving PMKB and proerythroblasts, the surface markers were coincident with the localization of peroxidase activity; glycophorin A was always absent from blasts which exhibited PPO activity localized in endoplasmic reticulum. Platelet glycoproteins were never expressed in any other cell lineage. The myeloid surface antigen was present on normal late neutrophilic promyelocytes after the cessation of myeloperoxidase synthesis. In some cases of M1 and M2 AML (FAB classification), labelling was identical to normal cells while in others the antigen appeared earlier than normal. Our findings show that the surface phenotype of blasts from non-lymphoid leukaemia and the intracellular peroxidase activity of a given cell type can be simultaneously demonstrated and analysed by electron microscopy.
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PMID:Simultaneous detection of membrane markers with monoclonal antibodies and peroxidatic activities in leukaemia: ultrastructural analysis using a new method of fixation preserving the platelet peroxidase. 609 46

The monoclonal antibody OKT9 (a known transferrin receptor antibody) and a monoclonal antibody to transferrin (ATfn) were used to localize the transferrin receptor and transferrin on marrow cells. After incubation of cell suspensions with the antibody, the cells were reacted with an affinity purified Fab fragment of goat anti-mouse IgG conjugated to horseradish peroxidase (GAM-HRP), which was in turn visualized by reaction with 3,3'-diaminobenzidine (DAB). Erythroblast cell surfaces stained intensely with OKT9-GAM-HRP-DAB, weaker staining was observed on reticulocyte surfaces, whereas erythrocyte surfaces lacked staining. Staining was present on surface caveolae, which often contained endogenous ferritin particles. Moderate to strong OKT9 staining was observed on less than 10% of presumed lymphoid cells. Monocytes, macrophages, promyelocytes, granulocytes, megakaryocytes and platelets consistently lacked OKT9 staining. ATfn-GAM-HRP-DAB staining of erythroid cells was similar to that observed with OKT9 staining; however, in contrast to the latter staining, ATfn stained the surfaces of megakaryocytes, platelets, monocytes and most lymphocytes. Promyelocytes stained weakly, whereas late granulocytes lacked staining. These results indicate that the T9 transferrin receptor (1) is largely confined to erythroid cells in marrow, (2) is diffusely distributed on the surface of early erythroid cells, (3) decreases with cell maturation, and (4) is lost when haemoglobin synthesis is completed. Transferrin appears in a similar distribution on erythroid cell surfaces but also appears to bind to some cell surfaces lacking the T9 receptor.
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PMID:Ultrastructural localization of the transferrin receptor and transferrin on marrow cell surfaces. 630 35

Treatment of murine erythroleukemia (MEL) cells with imidazole in the presence of dimethyl sulfoxide (Me2SO) has been shown to dissociate hemoglobin accumulation from commitment to terminal maturation. To explore the mechanism(s) of this effect, we studied iron transport and heme and hemoglobin synthesis in Me2SO-induced MEL cells that were then exposed to imidazole. Imidazole treatment (i) causes moderate inhibition of 125I-labeled transferrin binding to both control and Me2SO-treated MEL cells; (ii) markedly suppresses Me2SO-induced activation of iron uptake into MEL cells; (iii) markedly decreases the incorporation of iron into ferritin; and (iv) abolishes heme biosynthesis from [2-14C]glycine and hemoglobin accumulation in Me2SO-treated cells. Imidazole treatment does not inhibit other aspects of cellular maturation; cells treated with Me2SO in the presence or absence of imidazole exhibit similar changes in proliferative activity and protein synthesis and, as shown previously, in cell morphology. Inhibition of hemoglobin accumulation in MEL cells is reversible on withdrawal of imidazole but is not altered by exogenous hemin. These data indicate that commitment to terminal maturation is regulated independently from the systems for iron transport and heme biosynthesis during early phases of erythroid cell differentiation.
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PMID:Dissociation of iron transport and heme biosynthesis from commitment to terminal maturation of murine erythroleukemia cells. 632 76

Basic ferritin content of red cells has been evaluated with a simplified assay in subjects with various erythroid disorders. In 39 patients with iron deficiency anemia, red cell ferritin was significantly reduced compared with that of normal individuals. Thirty percent of these patients had low normal red cell ferritin content and the MCV for this group was significantly higher than that of patients with reduced red cell ferritin. The mean red cell ferritin of 30 subjects with the anemia of chronic disease was significantly reduced and patients in this group with normal red cell ferritin had higher plasma ferritin levels. In 14 patients with polycythemia vera, the mean red cell ferritin was significantly reduced and showed a positive correlation with the hemoglobin level and percent transferrin saturation. The red cell ferritin content of 9 individuals with acquired immune hemolytic anemia and 10 with acquired sideroblastic anemia was significantly elevated and, in subjects with immune hemolysis, showed a positive correlation with the reticulocyte count. These findings suggest a lack of discriminatory function for red cell ferritin in iron deficiency anemia and anemia of chronic disease. Evaluation of this parameter in the individual patient should take into account the presence of reticulocytosis.
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PMID:Basic ferritin content of red cells of patients with anemia and polycythemia vera. 652 7

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


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