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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The structure and properties of the iron-binding proteins transferrin, lactoferrin and transferrin are reviewed. Transferrin and lactoferrin are structurally similar, consisting of a single polypeptide chain and reversibly binding two iron atoms per molecule. Transferrin is found mainly in serum, whereas lactoferrin is found in neutrophils and in external secretions. Transferrin functions mainly as a donor of iron to cells, but there is no established iron-transport role for lactoferrin. Both these proteins may have antimicrobial activity as a result of their ability to sequester iron. Lactoferrin may act principally as a scavenger of iron in conditions where transferrin may not bind iron well, e.g. at low pH. Ferritin is a multisubunit protein capable of binding up to 4,000 iron atoms and serves principally as an iron-storage protein, though it may also serve to detoxify iron. In iron-rich tissues ferritin is largely degraded and the iron is converted to haemosiderin.
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PMID:Iron-binding proteins. 248 82

Fundamental aspects of iron metabolism relate to the dynamic processes of metal plasma transport as well as cell storage and efflux. Transferrin not only carries iron in the plasma but also delivers it to the various cells by binding to a diffuse specific cell receptor; it also acts by chelating cell iron. Ferritin co-operates by storing iron in the cell. By a still unknown regulatory mechanism, iron, from the ferritin pool, is redistributed in the cell to a cytosolic, easily chelatable, "transit" pool or to a degradative lysosomal hemosiderin pool from which it is slowly released outside the cell. Iron overload, such as that typical of hyperhemolysis or hemochromatosis, profoundly impairs its metabolism by saturating and/or altering transferrin and ferritin, by freeing iron from any regulated transport, thus allowing parenchymal deposition and damage. An important aspect still awaiting clarification relates to the different storage of excess iron in the parenchymal cells, as in hemochromatosis, or in the reticuloendothelial system such as in hemosiderosis. Studies using cellular models attempt to evaluate such differences in terms of altered properties of the iron proteins or their cell receptors, and of the different cell responsivity to non-transferrin iron. In the expectation of better knowledge, attention should be concentrated, from a clinical standpoint, on precise assessment of iron deposits in the tissues with the aim of preventing its excessive accumulation and parenchymal damage. In hemochromatosis, the risk of iron overload is evaluated by HLA typing.
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PMID:[Physiopathology of iron metabolism and hemochromatosis: interrelationships, assessment and pathogenesis of iron overload, screening]. 248 94

The known relationship between ethanol and the two main proteins of iron metabolism, transferrin and ferritin, are reviewed. Transferrin synthesis decreases in alcoholic cirrhosis, and increases in alcoholic fatty liver. In the latter case, its turnover is accelerated. Serum desialylated transferrin increases in chronic alcoholism and could be the best marker of heavy drinking. The increased uptake of desialylated transferrin by the liver could explain the development of hepatic siderosis in some alcoholics. Serum ferritin increases in chronic alcoholism, much more because of liver damage than in relation to iron stores. It is clear in this review that few experimental studies have been interested in the investigation of these relationships.
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PMID:[Interactions of alcohol and iron proteins]. 265 33

Total plasma iron turnover in man is about 36 mg/day. Transferrin is the iron transport protein of plasma, which can bind 2 atoms of iron per protein molecule, and which interacts with various cell types to provide them with the iron required for their metabolic and proliferative processes. All tissues contain transferrin receptors on their plasma membrane surfaces, which interact preferentially with diferric transferrin. In erythroid cells as well as certain laboratory cell lines, the removal of iron from transferrin apparently proceeds via the receptor-mediated endocytosis process. Transferrin and its receptor are recycled to the cell surface, whereas the iron remains in the cell. The mode of iron uptake in the hepatocyte, the main iron storage tissue, is less certain. The release of iron by hepatocytes, as well as by the reticuloendothelial cells, apparently proceeds nonspecifically. All tissues contain the iron storage protein ferritin, which stores iron in the ferric state, though iron must be in the ferrous state to enter and exit the ferritin molecule. Cellular cytosol also contains a small-molecular-weight ferrous iron pool, which may interact with protoporphyrin to form heme, and which apparently is the form of iron exported by hepatocytes and macrophages. In plasma, the ferrous iron is converted into the ferric form via the action of ceruloplasmin.
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PMID:Biochemistry of nonheme iron in man. I. Iron proteins and cellular iron metabolism. 266 99

In previous studies, antitransferrin receptor antibody 42/6 inhibited growth of normal granulocyte/macrophage progenitors and some malignant myeloid cells. In these studies, leukemia cell lines cultured without serum and fresh leukemia cells were used to investigate the roles of Fe, transferrin receptors, and transferrin in leukemia cell growth, and mechanisms of 42/6 inhibition and resistance. HL60 and KG-1 leukemia cells grown in serum-free medium were inhibited by 42/6. In contrast to results in fetal calf serum (FCS), soluble Fe (ferric nitriloacetate) reversed 42/6 growth inhibition of serum-free HL60 cells. When HL60 cells were adapted for growth in serum-free, transferrin-free medium, they became refractory to 42/6 growth inhibition. By using radiolabeled transferrin and 42/6, HL60 cells cultured in FCS and transferrin displayed similar quantities of transferrin receptors (29,000-30,000/cell) and similar Kd's (3.8-4.9 X 10(-9) M). Cells grown in transferrin-free medium showed a similar Kd (3.1 X 10(-9) M), but fewer transferrin binding sites (5,000/cell). Transferrin-independent cells contained a log higher concentration of intracellular ferritin. For both FCS and serum-free HL60 cells, calculated affinities for 42/6 were lower (5.7-10.0 X 10(-9) M), but the number of binding sites was three- to fourfold higher. To investigate further the relationship between receptor display and antibody inhibition in proliferating normal and malignant myeloid cells, simultaneous immunofluorescence was used to determine the cell cycle status of transferrin receptor-positive cells. Malignant cells in S + G2/M displayed approximately 50% of the amount of transferrin receptors detected in normal dividing colony-stimulating factor-stimulated marrow cells. Receptor display by dividing cells from two patients with acute nonlymphocytic leukemia was variable. When HL60 cells were exposed to dimethyl sulfoxide, transferrin receptor display decreased, and 42/6 growth inhibition was abrogated or greatly diminished. The presence of 42/6 did not prevent dimethyl sulfoxide-induced HL60 differentiation in serum-containing or serum-free cultures. We conclude that human leukemia cells require Fe for growth and that 42/6 inhibits transferrin-dependent cells by Fe deprivation. Some dividing normal and differentiating malignant cells display reduced transferrin receptors, and can also escape antibody inhibition. The increased ferritin levels and decreased transferrin receptors in transferrin-independent HL60 cells confirm the inverse relationship between cell ferritin content and transferrin receptor display. These studies indicate a critical role for Fe in leukemia cell growth and possible roles in cellular differentiation.
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PMID:Role of transferrin, Fe, and transferrin receptors in myeloid leukemia cell growth. Studies with an antitransferrin receptor monoclonal antibody. 298 53

Transferrin (Tf) and ferritin (Fr), the proteins which participate in iron transport, were examined to determine their fluctuation during pregnancy and their localization in human placental tissue, and the iron transport mechanism between mother and fetus was discussed. The main results are as follows: Maternal serum ferritin (SFr) decreased remarkably and the maternal total iron binding capacity (TIBC) increased gradually as pregnancy progressed. Maternal serum iron (SI), SFr and TIBC at delivery were 59.8 +/- 26.2 micrograms/dl, 9.6 +/- 7.2 ng/ml and 495.2 +/- 100.3 micrograms/dl, and cord blood SI, SFr and TIBC were 161.5 +/- 42.1 micrograms/dl, 160.5 +/- 67.2 ng/ml and 177.7 +/- 33.9 micrograms/dl, respectively. Peroxidase conjugating antibody method revealed the localization of Tf on the microvillous surface of syncytiotrophoblasts, and the localization of Fr in all layers of trophoblasts, especially in the neighborhood of the surface. Ferritin content of the placenta in the 1st, 2nd and 3rd trimesters was 0.07 +/- 0.03, 0.18 +/- 0.03 and 0.25 +/- 0.09 (micrograms/mg protein), respectively. These results indicate that iron is transferred from the mother to the fetus by the placental active function, and Tf receptor and Fr on trophoblasts participate in the adequate placental iron transport.
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PMID:Studies on the placental transport mechanism for iron. 298 75

Transferrin, its receptor and the entry of iron into the cell have sprung into prominence because of recent evidence that proliferation of various cell types involves regulation of this sequence of events, as evidenced especially by changes in receptor number. A third component functionally linked to transferrin and its receptor is the intracellular iron-storage protein, ferritin, which ensures against toxic levels of free ferrous iron, which might otherwise cause peroxidative damage to cell membranes and other cell structures (1). In this article, we shall focus on interactions between these three proteins of iron exchange, their roles in homeostasis and especially their role in relation to the liver which is a major organ of iron storage.
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PMID:Transferrin and its receptor: their roles in cell function. 299 49

Transferrin is taken up by receptor-mediated endocytosis into intracellular vesicles and tubules, and then recycles rapidly to the plasma membrane (diacytosis). We applied double-label cytochemistry to study whether the recycling structures containing transferrin fuse with the intracellular membranous structures that deliver newly synthesized membrane glycoproteins from the ER to the plasma membrane (exocytosis) or whether they remain independent. KB and Vero cells were infected with the temperature-sensitive transport mutant 0-45 of vesicular stomatitis virus (VSV). Temperature-regulated exocytosis of membrane glycoprotein "G" occurred simultaneously with diacytosis of transferrin. The exocytic "G" protein, as detected by immunoperoxidase electron microscopy, passed through the cisternal Golgi stacks and vacuolar, tubular, vesicular, and pit-like structures of the Golgi system. A transferrin-ferritin conjugate used in ultrastructural double-label experiments was detected in diacytic vesicles and tubules that accumulated in the proximal (trans-reticular) Golgi area of the cell. The ferritin-labeled vesicles/tubules were often close to and intermixed with the VSV-"G" containing membranous structures, but in most cases at early times (15-20 min) the transferrin and VSV-"G" containing vesicular structures remained distinct. At later times (30-45 min), the two labels were occasionally found in the same structures. These results indicate that rapid recycling of endocytosed materials and exocytosis of membrane glycoproteins to the cell surface usually occur in distinct vesicles, possibly along the same general morphologic exit pathway.
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PMID:Comparison of the intracellular pathways of transferrin recycling and vesicular stomatitis virus membrane glycoprotein exocytosis by ultrastructural double-label cytochemistry. 302 94

Transferrin and ferritin endocytosis and exocytosis by guinea-pig reticulocytes were studied using incubation with pronase at 4 degrees C to distinguish internalized and membrane-bound protein. Internalization of both transferrin and ferritin occurred in a time- and temperature-dependent fashion. Transferrin endocytosis was more rapid than that of ferritin. Transferrin binding to receptors was not altered, but transferrin endocytosis was decreased in the presence of ferritin. Iron accumulation from transferrin was inhibited by ferritin to a greater extent than could be accounted for by the decreased rate of endocytosis. In pulse-chase experiments, almost all of the transferrin was released intact from reticulocytes, but only about 50% of the total internalized ferritin was released, of which 85% was intact. The endocytosis of transferrin by rabbit reticulocytes was 2- to 2.5-times faster than guinea-pig reticulocytes. These data suggest that ferritin and transferrin are internalized by receptor-mediated endocytosis, possibly involving the same coated pits and vesicles, but that the proteins are recycled only partly in common.
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PMID:Transferrin and ferritin endocytosis and recycling in guinea-pig reticulocytes. 303 46

The relationship between the number of units of blood transfused and indicators of iron status in 37 patients with sickle cell anaemia (Hb SS), SC disease (Hb SC) or S beta-thalassaemia has been studied. The correlation coefficient between serum ferritin and the number of units transfused was good (r = 0.86), provided that ferritin samples taken within one week following a crisis were excluded. The relationship of transfusion history to serum ferritin in the steady state showed a similar relationship to that previously observed for other multiply transfused patients. The serum ferritin taken within 7 days of a painful crisis was significantly greater than the serum ferritin from the same patients in the steady state (p less than 0.025). The serum alanine transaminase did not rise as consistently as the serum ferritin during crises; it correlated with the serum ferritin but not the transfusion burden in the steady state. Transferrin iron saturation correlated less clearly with transfusion history than serum ferritin (r = 0.62). Patients who had received exchange transfusions were less likely to be iron-overloaded (ferritin increment per unit of blood = 9.9 +/- 3.8 micrograms/l) than patients who had received an equivalent number of units by conventional transfusion (ferritin increment per unit of blood transfused = 25.1 +/- 2.42 micrograms/l).
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PMID:Transfusion and exchange transfusion in sickle cell anaemias, with particular reference to iron metabolism. 312 Apr 72


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