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

We studied serum transferrin and ferritin concentrations in relation to individual body growth, stage of puberty, blood hemoglobin, and red blood cell iron (RBCI) in 60 prepubertal or early pubertal boys at 3-mo intervals for 18 mo. One-third of the boys had increased serum transferrin concentrations and almost all had decreased ferritin concentrations during the followup. No change in mean transferrin was observed but the individual 18-mo increments in transferrin correlated positively with the increments in hemoglobin (r = 0.55, P < 0.001) and in estimated RBCI (r = 0.31, P = 0.02). Serum transferrin remained stable at different genital stages, but ferritin was lower in the pubertal than in the prepubertal boys. Transferrin concentrations at 18 mo correlated positively with the preceding weight velocities. The rise in transferrin did not lead to an increase in iron-deficiency anemia. In contrast, transferrin rose in boys whose hemoglobin increased. In pubertal boys with relatively ample iron status, serum transferrin may be an indicator of increased availability of iron for erythropoiesis. The declining ferritin concentration indicates that part of the extra iron is mobilized through redistribution from stores to red blood cell mass and is generally associated with greatly increasing absorption. Thus, the pubertal changes in transferrin and ferritin are not necessarily indications of iron deficiency.
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PMID:Serum transferrin and ferritin in pubertal boys: relations to body growth, pubertal stage, erythropoiesis, and iron deficiency. 856 Oct 58

Oligodendrocytes are the predominant iron-containing cells in the brain. Iron-containing oligodendrocytes are found near neuronal cell bodies, along blood vessels, and are particularly abundant within white matter tracts. Iron-positive cells in white matter are present from birth and eventually reside in defined patches of cells in the adult. These patches of iron-containing cells typically have a blood vessel in their center. Ferritin, the iron storage protein, is also expressed early in development in oligodendrocytes in a regional and cellular pattern similar to that seen for iron. Recently, the functionally distinct subunits of ferritin have been analyzed; only heavy (H)-chain ferritin is found in oligodendrocytes early in development. H-ferritin is associated with high iron utilization and low iron storage. Consistent with the expression of H-ferritin is the expression of transferrin receptors (for iron acquisition) on immature oligodendrocytes. Transferrin protein accumulation and mRNA expression in the brain are both dependent on a viable population of oligodendrocytes and may have an autocrine function to assist oligodendrocytes in iron acquisition. Although apparently the majority of oligodendrocytes in white matter tracts contain ferritin, transferrin, and iron, not all of them do, indicating that there is a subset of oligodendrocytes in white matter tracts. The only known function of oligodendrocytes is myelin production, and both a direct and indirect relationship exists between iron acquisition and myelin production. Iron is directly involved in myelin production as a required co-factor for cholesterol and lipid biosynthesis and indirectly because of its requirement for oxidative metabolism (which occurs in oligodendrocytes at a higher rate than other brain cells). Factors (such as cytokines) and conditions such as iron deficiency may reduce iron acquisition by oligodendrocytes and the susceptibility of oligodendrocytes to oxidative injury may be a result of their iron-rich cytoplasm. Thus, the many known phenomena that decrease oligodendrocyte survival and/or myelin production may mediate their effect through a final common pathway that involves disruptions in iron availability or intracellular management of iron.
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PMID:Relationship of iron to oligodendrocytes and myelination. 877 76

All organs including the brain contain iron, and the proteins involved in iron uptake (transferrin and transferrin receptor) and intracellular storage (ferritin). However, because the brain resides behind a barrier and has a heterogeneous population of cells, there are aspects of its iron management that are unique. Iron management, the timely delivery of appropriate amounts of iron, is crucial to normal brain development and function. Mismanagement of cellular iron can result not only in decreased metabolic activity but increased vulnerability to oxidative damage. There is regional specificity in cell deposition of iron and the iron regulatory proteins. However, the sequestration of iron in the brain seems primarily the responsibility of oligodendrocytes, as these cells contain most of the stainable iron in the brain. Transferrin, the iron-mobilizing protein, is also found predominantly in these cells. The transferrin receptor is abundantly expressed on blood vessels, large neurons in the cortex, striatum, and hippocampus, and is also present on oligodendrocytes and astrocytes. Ferritin, the intracellular iron storage protein, consists of 2 subunits which are functionally distinct, and we provide evidence in this report that the cellular distribution of the ferritin subunits is also distinct. In addition, changes in the cellular distribution of iron and its associated regulatory proteins occur in Alzheimer's disease. Neuritic plaques contain relatively large amounts of stainable iron, and the surrounding cells robustly immunostain for ferritin and the transferrin receptor. Analysis of the cellular distribution of iron indicates the different levels of requirement of iron in the brain by different cell types and should ultimately elucidate how cells acquire and maintain this essential component of oxidative metabolism. In addition, changes in the ability of cells to deliver and manage iron may provide insight into altered metabolic activity with age and disease as well as identify cell populations at risk for iron-induced oxidative stress.
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PMID:Cellular management of iron in the brain. 884 43

Genetic hemochromatosis is an autosomal recessive disease characterized by increased intestinal iron absorption and consequent tissue iron overload. The hemochromatosis gene has been localized on the short arm of chromosome 6, in close proximity to the HLA locus, but has yet to be identified. Neither the gene product nor the pathogenetic defect have been characterized. Clinical manifestations vary according to the degree of iron overload, ranging from the asymptomatic state to the features of cirrhosis and hepatocellular carcinoma. Early diagnosis remains essential, since the survival of patients without established cirrhosis is comparable to that of the general population. Transferrin saturation and ferritin levels are suggestive of the diagnosis, but measurement of the hepatic iron concentration still remains the gold standard, despite the utilization of computerized tomography and magnetic resonance imaging. Routine phlebotomies constitute the principal therapeutic option, despite the recent preliminary data on oral iron chelators.
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PMID:Genetic hemochromatosis: pathogenesis, diagnosis, and therapy. 890 16

Iron is transported in the blood plasma, mainly bound to transferrin, but in abnormal conditions other iron containing compounds may become important. These include ferritin, haemopexin-haem, haptoglobin-haemoglobin and non-specific non-transferrin-bound iron, all of which are taken up from the circulation by the liver. Transferrin-bound iron can be used by all types of cells in amounts that depend on their complement of transferrin receptors. Immature erythroid cells are the most active in this function. Investigations using reticulocytes as an example of erythroid cells have demonstrated the presence of two mechanisms for the uptake of ferrous iron. One, a high affinity process disappears as reticulocytes mature. It probably represents the mechanism by which iron derived from transferrin is transported into the cytosol after receptor-mediated endocytosis of the iron-transferrin complex. The other mechanism has a lower affinity for iron, is retained when reticulocytes mature and is probably associated with Na+ transport across the cell membrane. The physiological characteristics of the two iron transport processes and the evidence for the above conclusions are summarized in the present paper.
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PMID:Cellular iron processing. 898 22

Microcytosis, hypochromasia, and low mean corpuscular hemoglobin are frequent hematologic abnormalities in dogs with portosystemic vascular anomalies (PSVA). The relationship of iron status to these abnormalities is unclear. We evaluated iron status and hematologic and biochemical parameters in dogs with congenital PSVA before (25 dogs) and after (11 dogs) partial ligation of the vascular anomaly. Serum iron concentration and total iron binding capacity were subnormal in 56% and 20% of dogs with PSVA, respectively. Transferrin saturation was normal in 68%, decreased in 20%, and increased in 12% of the dogs. Plasma ferritin concentration was either normal (56%) or high (44%), and was not associated with increases in ceruloplasmin concentration. Hepatic stainable iron was increased in 10 of 16 dogs. Mean corpuscular volume (MCV), mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration were decreased in more than 60% of dogs with PSVA. Serum biochemical abnormalities included high bile acid concentration and alanine transaminase (ALT) and alkaline phosphatase (ALP) activities; and low urea, creatinine, cholesterol, and total protein concentrations. Serum iron concentration and clinical status (normal or PSVA) significantly influenced MCV (P = .003 and P < .001, respectively), whereas age, ceruloplasmin, ferritin, cholesterol, bile acids, and total iron binding capacity did not. Partial ligation of PSVA was associated with resolution of clinical signs and the return to normal of iron status and all clinicopathologic abnormalities, except total fasting bile acid concentrations. These findings indicate that iron status is frequently abnormal in dogs with PSVA and that low serum iron concentration appears to be related to the development of microcytosis. The normalization of iron status and clinicopathologic abnormalities after treatment suggests that they are direct consequences of PSVA.
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PMID:Iron status and erythrocyte volume in dogs with congenital portosystemic vascular anomalies. 913 78

The effect of the key iron homeostasis proteins transferrin and ferritin on the activity of partially purified brain calcium-calmodulin-dependent phosphodiesterase (CaM-PDE, EC 3.4.1.17) were studied. Transferrin and ferritin were found to be potent natural activators of CaM-PDE. The key factor determining the degree of activation by these proteins is their saturation with iron: apotransferrin activated CaM-PDE 6-7-fold; iron-poor brain ferritin and liver apoferritin (taken for comparison) activated the enzyme 4-5- and 2-fold, respectively. Diferric transferrin and iron-rich liver ferritin had no effects on the enzyme activity. Transferrin and ferritin (both in apo- and iron-saturated forms) did not change the activity of calmodulin-phosphodiesterase complex. The data suggest that apotransferrin and iron-poor transferrin are involved in the regulation of cyclic nucleotide content in nervous tissue.
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PMID:Transferrin and ferritin modulate the activity of brain calcium-calmodulin-dependent phosphodiesterase. 915 70

Anemia of chronic renal failure (CRF) prior to initiation of dialysis is an important cause of morbidity and requires early therapeutic intervention. The current study was designed to investigate the efficacy and tolerability of a therapeutic algorithm for anemia of CRF in pre-dialysis patients which is based on low dose once-a-week subcutaneous (s.c.) administration of recombinant human erythropoietin (r-HuEPO). Thirty-one patients participated in a prospective open-label multicenter study. At baseline, hemoglobin was 8.8+/-0.1 g/dl, transferrin saturation 27+/-2%, ferritin 207+/-28 ng/ml and serum creatinine 4.7+/-0.2 mg/dl. Treatment with r-HuEPO was started at a fixed s.c. dose of 4,000 units once weekly, irrespective of body weight, and titrated upwards or downwards according to a predetermined algorithm. Hemoglobin rose to levels >10 g/dl within 8 weeks and remained stable throughout the remaining period of the study. By week 24, most patients required <or =4,000 units/week as maintenance dose. Transferrin saturation and ferritin concentration tended to fall during the course of r-HuEPO treatment, despite iron supplementation. There was no change in white blood cell or platelet count. Eight patients required an increase in antihypertensive therapy, but blood pressure remained well-controlled. Twelve patients failed to complete the full length of the study, 7 of them because dialysis had to be initiated. The rate of decline in kidney function, however, was not altered by r-HuEPO. We conclude that the proposed therapeutic algorithm is practical, efficacious, safe, and cost-effective.
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PMID:Proposed therapeutic algorithm for the treatment of anemia of chronic renal failure in pre-dialysis patients with low dose once weekly subcutaneous r-HuEPO. Multicenter Study Group, Israel. 920 16

Iron uptake by mammalian cells is mediated by the binding of serum Tf to the TfR. Transferrin is then internalized within an endocytotic vesicle by receptor-mediated endocytosis and the Fe released from the protein by a decrease in endosomal pH. Apart from this process, several cell types also have other efficient mechanisms of Fe uptake from Tf that includes a process consistent with non-specific adsorptive pinocytosis and a mechanism that is stimulated by small-Mr Fe complexes. This latter mechanism appears to be initiated by hydroxyl radicals generated by the Fe complexes, and may play a role in Fe overload disease where a significant amount of serum non-Tf-bound Fe exists. Apart from Tf-bound Fe uptake, mammalian cells also possess a number of mechanisms that can transport Fe from small-Mr Fe complexes into the cell. In fact, recent studies have demonstrated that the membrane-bound Tf homologue, MTf, can bind and internalize Fe from 59Fe-citrate. However, the significance of this Fe uptake process and its pathophysiological relevance remain uncertain. Iron derived from Tf or small-Mr complexes is probably transported into mammalian cells in the Fe(II) state. Once Fe passes through the membrane, it then becomes part of the poorly characterized intracellular labile Fe pool. Iron in the labile Fe pool that is not used for immediate requirements is stored within the Fe-storage protein, ferritin. Cellular Fe uptake and storage are coordinately regulated through a feedback control mechanism mediated at the post-transcriptional level by cytoplasmic factors known as IRP1 and IRP2. These proteins bind to stem-loop structures known as IREs on the 3 UTR of the TfR mRNA and 5 UTR of ferritin and erythroid delta-aminolevulinic acid synthase mRNAs. Interestingly, recent work has suggested that the short-lived messenger molecule, NO (or its by-product, peroxynitrite), can affect cellular Fe metabolism via its interaction with IRP1. Moreover, NO can decrease Fe uptake from Tf by a mechanism separate to its effects on IRP1, and NO may also be responsible for activated macrophage-mediated Fe release from target cells. On the other hand, the expression of inducible NOS which produces NO, can be stimulated by Fe chelators and decreased by the addition of Fe salts, suggesting that Fe is involved in the control of NOS expression.
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PMID:The molecular mechanisms of the metabolism and transport of iron in normal and neoplastic cells. 932 34

Early detection of iron sufficiency at the level of the erythropoietic cell is necessary to optimize management of uremic anemia with recombinant human erythropoietin (rHuEPO). "Absolute" and "functional" iron deficiency are the most important factors causing resistance to administered rHuEPO. Transferrin saturation and serum ferritin measurements have been noted to be insensitive and inaccurate measures to detect functional iron deficiency. Recently, the reticulocyte hemoglobin content (CHr) has been shown to be a sensitive and specific indicator of functional iron deficiency in nondialysis patients treated with rHuEPO. The purpose of this study is to compare CHr with currently used indices of iron sufficiency in rHuEPO-treated hemodialysis (HD) patients. In study 1, 364 stable HD patients were studied at two outpatient dialysis centers. CHr was normally distributed, with a mean value of 28.3 pg, and was consistent over two consecutive monthly samples in each center. CHr was weakly but consistently correlated with transferrin saturation and serum ferritin. CHr and reticulocyte number were inversely correlated with red blood cell (RBC) number, suggesting that the erythropoietic stimulus of routinely administered rHuEPO may have resulted in functional iron deficiency. Month-to-month changes in CHr correlated weakly with changes in serum iron and percent transferrin saturation, but not at all with changes in serum ferritin. When we analyzed those patients with baseline CHr less than 26 pg, a level strongly suggestive of functional iron deficiency, these correlations strengthened, and in addition, month-to-month changes in CHr correlated strongly and directly with concomitant changes in RBC count, hemoglobin, and hematocrit, suggesting that rising CHr was indicative of an erythropoietic response. In study 2, 79 patients received a single-dose infusion of 500 mg iron dextran. After intravenous iron, CHr rose within 48 hours, peaked at 96 hours, and then fell toward baseline. Patients who were iron deficient by standard measures (serum ferritin < 100 ng/mL or transferrin saturation less than 20%) had a greater and a sustained CHr response to intravenous iron dextran. A CHr less than 28 pg at baseline predicted functional iron deficiency, defined as a corrected reticulocyte increase of greater than 1% to iron dextran, more accurately than transferrin saturation, ferritin, or their combination. Eighty-two percent of individuals who were iron deficient at baseline responded to intravenous iron with an increase in CHr of greater than 2 pg. Sixty percent of patients who were iron sufficient by usual iron indices also responded to intravenous iron with a CHr rise of greater than 2 pg, suggesting that they were, in fact, functionally iron deficient despite "normal" conventional iron parameters. We conclude that CHr may be a more sensitive marker of functional iron deficiency in rHuEPO-treated hemodialysis patients than percent transferrin saturation and ferritin, particularly in those with "normal" conventional iron parameters.
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PMID:Reticulocyte hemoglobin content predicts functional iron deficiency in hemodialysis patients receiving rHuEPO. 939 41


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