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)

The urinary excretion of iron has been studied in 23 cases of iron overload (20 thalassemia major, 2 pure red cell aplasia, 1 congenital sideroblastic anemia) after 12 hour subcutaneous infusions of 0.5 g, 1 g, 2 g and 3 g of desferrioxamine (D). The urinary excretion of iron was correlated with the dose of D and the serum ferritin. Continuous subcutaneous infusion of 0.5 g and 1 g D over 12 hours increased the mean urinary iron excretion from 6.6 to 12 mg/day and 9.9 to 18 mg/day respectively compared with intramuscular injection of a similar dose. The test doses of D have been used to determine the dose of D necessary to balance the iron received in transfusion and the iron excreted in the urine. Five children treated for between 7 and 12 months demonstrated that the treatment is effective. Serum ferritin levels decreased and the children were in negative iron balance. Using a portable constant infusion pump subcutaneous infusions can be given at home.
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PMID:[Treatment of iron overload due to repeated transfusions with subcutaneous infusions of desferrioxamine (author's transl)]. 740 38

Chloramphenicol is an antibiotic that consistently suppresses the bone marrow and induces sideroblastic anemia. It is also a rare cause of aplastic anemia. These toxicities are thought to be related to mitochondrial dysfunction, since chloramphenicol inhibits mitochondrial protein synthesis. We hypothesized that chloramphenicol-induced mitochondrial impairment alters the synthesis of ferritin and the transferrin receptor. After treating K562 erythroleukemia cells with a therapeutic dose of chloramphenicol (10 microg/ml) for 4 days, there was a marked decrease in cell surface transferrin receptor expression and de novo ferritin synthesis associated with significant decreases in cytochrome c oxidase activity, ATP levels, respiratory activity, and cell growth. Decreases in the transferrin receptor and ferritin were associated with reduced and unchanged message levels, respectively. The mechanism by which mitochondrial dysfunction alters these important proteins in iron homeostasis is not clear. A global decrease in synthetic processes seems unlikely, since the expression of the cellular adhesion proteins VLA4 and CD58 was not significantly decreased by chloramphenicol, nor were the message levels of beta-actin or ferritin. The alterations were not accompanied by changes in binding of the iron response protein (IRP) to the iron-responsive element (IRE), although cytosolic aconitase activity was reduced by 27% in chloramphenicol-treated cells. A disturbance in iron homeostasis due to alterations in the transferrin receptor and ferritin may explain the hypochromic-microcytic anemia and the accumulation of nonferritin iron in the mitochondria in some individuals after chloramphenicol therapy. Also, these studies provide evidence of a link between mitochondrial impairment and iron metabolism in K562 cells.
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PMID:Chloramphenicol-induced mitochondrial dysfunction is associated with decreased transferrin receptor expression and ferritin synthesis in K562 cells and is unrelated to IRE-IRP interactions. 1043 Jan 73

We encountered two patients who presented with hypochromic-microcytic anemia and were refractory to iron therapy. The symptoms were suggestive of anemia of chronic disease (ACD); however, there was no evidence of any such disease, either inflammatory or malignant. These patients were reminiscent of patients originally described as having primary defective iron reutilization. The hematologic picture consisted of hypochromic-microcytic anemia, low serum iron, low to normal iron binding capacity, high serum ferritin, and increased bone marrow iron in the absence of ringed sideroblasts. These patients had symptomatic anemia and received danazol (200 mg orally) three times per day to which they responded very well with an increase of approximately 3 g in the hemoglobin concentration over 1 year and amelioration of their symptoms. Danazol was well tolerated and did not cause any virilizing side effects. Doses were lowered in maintenance after 1 year to 200 mg once per week, and responses were sustained up to 36 months of follow-up duration. In the differential diagnosis of hypochromic-microcytic anemia, especially in postmenopausal women, one has to consider this type of treatable anemia when more common types such as iron deficiency, chronic inflammation, malignancy, sideroblastic anemia, or thalassemia have been ruled out.
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PMID:Treatment of primary defective iron-reutilization syndrome: revisited. 1098 70

Hemochromatosis is characterized by an excessive iron deposit in different tissues. Cardiac involvement may be observed in one third of the patients due to hemochromatosis and occurs as a consequence of ferritin accumulation in the heart which on one hand induces alterations in systolic and diastolic ventricular function and on the other hand, an arrythmogenic substrate. The clinical manifestations can be indistinctly related to atrial tachyarrhythmia, ventricular tachyarrhythmia, atrio-ventricular blockade and congestive heart failure, with the first being the most frequent. We present the case of one patient with secondary hemochromatosis to repeated transfusions due to sideroblastic anemia with cardiac involvement, whose initial heart manifestations were recurrent atrial tachyarrhythmia and sustained ventricular tachycardia with syncope for which an automatic defibrillator was implanted.
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PMID:[Ventricular tachycardia and cardiac hemochromatosis]. 1170 44

Transfusion of RBC units, the only current treatment for many myelodysplastic syndromes, and excess intestinal absorption of Fe related to dyserythopoiesis often result in iron overload. This condition is associated with high rates of morbidity and mortality. High-risk patients include those with refractory anemia, sideroblastic anemia, 5q-syndrome, patients with a good prognosis (low or lower intermediate international prognosis score), patients having received over 100 RBC units, and patients under the age of 70. Deferoxamine, while it can prevent iron overload, is a strenuous treatment requiring 8-to-12 hour-overnight subcutaneous injections. When patients comply with the regimen, it efficiently prevents mortality due to iron overload, but must be implemented early in the disorder, usually before transfusing 20 RBC concentrates. A simple way of monitoring iron overload is to measure seric ferritin levels and record the number of RBC concentrates. The chelating treatment should be modulated according to age, MDS type, international prognosis score, number of RBC units received, ferritin levels, and most of all, patient tolerance. The direct subcutaneous approach is currently being evaluated by the French Group for Myelodysplasias for its efficiency to prevent disorders, but seems to be both efficient and well complied with (a national protocol is under way). The recent findings on the proteins implied in iron recycling by macrophages after destruction of RBCs, may in the long term, enable us to manage patients with less burdensome treatments and more effective new oral chelates.
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PMID:[Iron overload and myelodysplastic syndromes]. 1172 96

The sideroblastic anemias are characterized by ring sideroblasts, that is, red cell precursors with mitochondrial iron accumulation. We therefore studied the expression of mitochondrial ferritin (MtF) in these conditions. Erythroid cells from 13 patients with refractory anemia with ring sideroblasts (RARS) and 3 patients with X-linked sideroblastic anemia (XLSA) were analyzed for the distribution of cytoplasmic H ferritin (HF) and MtF using immunocytochemical methods. We also studied 11 healthy controls, 5 patients with refractory anemia without ring sideroblasts (RA), and 7 patients with RA with excess of blasts (RAEB). About one fourth of normal immature red cells, mostly proerythroblasts and basophilic erythroblasts, showed diffuse cytoplasmic positivity for HF, but very few were positive for MtF (0%-10%). Similar patterns were found in anemic patients without ring sideroblasts. In contrast, many erythroblasts from patients with sideroblastic anemia (82%-90% in XLSA and 36%-84% in RARS) were positive for MtF, which regularly appeared as granules ringing the nucleus. Double immunocytochemical staining confirmed the different cellular distribution of HF and MtF. There was a highly significant relationship between the percentage of MtF(+) erythroblasts and that of ring sideroblasts (Spearman R = 0.90; P <.0001). Reverse transcription-polymerase chain reaction studies demonstrated the presence of MtF mRNA in circulating reticulocytes of 2 patients with XLSA but not in controls. These findings suggest that most of the iron deposited in perinuclear mitochondria of ring sideroblasts is present in the form of MtF and that this latter might be a specific marker of sideroblastic anemia.
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PMID:Mitochondrial ferritin expression in erythroid cells from patients with sideroblastic anemia. 1240 66

Mitochondrial ferritin (MtF) is a novel H-type ferritin encoded by an intronless gene on chromosome 5q23.1. The protein is synthesized as a precursor of about 30 kDa that is targeted to mitochondria by a leader sequence of 60 amino acids. This leader is proteolytically removed inside the mitochondria and the resulting 22 kDa subunit forms typical ferritin shells. These shells have ferroxidase activity and are therefore likely to sequester potentially harmful free iron. However, this may be a limited function since MtF has a very restricted tissue expression. High amounts are found in testis but only very low levels are found in iron storage organs. The levels of MtF appear to correlate more with mitochondrial abundance than with iron metabolism. MtF does not seem to be an obligatory intermediate in transfer of free iron to heme and other iron compounds in mitochondria. However, its level increases dramatically in sideroblastic anemia when heme synthesis is disrupted. This increased synthesis does not appear to involve the classical translational control since MtF mRNA lacks an apparent iron response element. In transfected HeLa cells added iron is incorporated as quickly into MtF as into cytosolic ferritin. In addition, increased levels of MtF cause a redistribution of iron from cytosol to mitochondria and this effect is enhanced by iron chelation. Thus high levels of MtF result in an iron deficient phenotype in cytosol with decreased expression of ferritin and increased expression of transferrin receptor. This avidity for iron may explain why MtF levels are maintained at low levels in most normal cells. The regulation of MtF expression and possible therapeutic applications of MtF in neurological disorders involving increased iron deposition are topics for future research.
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PMID:Mitochondrial ferritin: a new player in iron metabolism. 1254 28

Mitochondrial ferritin (MtF) is structurally and functionally similar to the cytosolic ferritins, molecules designed to store and detoxify cellular iron. MtF expression in human and mouse is restricted to the testis and few tissues, and it is abundant in the erythroblasts of patients with sideroblastic anemia, where it is thought to protect the mitochondria from the damage caused by iron loading. Mitochondria iron overload occurs also in cells deficient in frataxin, a mitochondrial protein involved in iron handling and implicated in Friedreich ataxia. We expressed human MtF in frataxin-deficient yeast cells, a well-characterized model of mitochondrial iron overload and oxidative damage. The human MtF precursor was efficiently imported by yeast mitochondria and processed to functional ferritin that actively sequestered iron in the organelle. MtF expression rescued the respiratory deficiency caused by the loss of frataxin protecting the activity of iron-sulfur enzymes and enabling frataxin-deficient cells to grow on non-fermentable carbon sources. Furthermore, MtF expression prevented the development of mitochondrial iron overload, preserved mitochondrial DNA integrity and increased cell resistance to H2O2. The data show that MtF can substitute for most frataxin functions in yeast, suggesting that frataxin is directly involved in mitochondrial iron-binding and detoxification.
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PMID:The expression of human mitochondrial ferritin rescues respiratory function in frataxin-deficient yeast. 1528 5

Erythroid dysplasia is the pathologic hallmark of myelodysplastic syndromes (MDS). To develop a quantitative flow-cytometry approach to its evaluation, we analyzed the expression of CD71, CD105, cytosolic H-ferritin (HF), cytosolic L-ferritin (LF) and mitochondrial ferritin (MtF) in erythroblasts from 104 MDS patients, 69 pathologic control patients and 19 healthy subjects. Six-parameter, 4-color flow cytometry was employed, and data were expressed as mean fluorescence intensity. Compared with pathologic and healthy controls, MDS patients had higher expression of HF (P < 0.001) and CD105 (P < 0.001), and lower expression of CD71 (P < 0.001). MtF was specifically detected in MDS with ringed sideroblasts, and there was a close relationship between its expression and Prussian blue staining (r = 0.89, P < 0.001). In vitro cultures of myelodysplastic hematopoietic progenitors showed that both HF and MtF were expressed at a very early stage of erythroid differentiation, and that MtF expression is specifically related to mitochondrial iron loading. A classification function based on expression levels of HF, CD71 and CD105 allowed us to correctly classify > 95% of MDS patients. This flow-cytometry approach provides an accurate quantitative evaluation of erythroid dysplasia and allows a reliable diagnosis of sideroblastic anemia, and may therefore be a useful tool in the work-up of patients with MDS.
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PMID:Flow cytometry evaluation of erythroid dysplasia in patients with myelodysplastic syndrome. 1649 94

In this retrospective study, we report the results of the association of a combined phlebotomy program and chelation in hereditary sideroblastic anemia (HSA) to reduce iron overload after bone marrow transplantation (BMT). A male HSA patient, not responding to pyridoxine treatment, was submitted to successful allogeneic BMT. As there was a persistence of a tissue iron overload, a regular phlebotomy program was started followed by chelation. A significant decrease of iron burden was obtained using a combined treatment with deferoxamine (DFO) and deferiprone (L1) in addition to the phlebotomy program. A 10-year follow-up shows a marked decrease in the concentration of serum ferritin, non-transferrin-bound iron (NTBI), liver iron and normal hemoglobin (Hb), which allows the patient to reach and maintain a good quality of life.
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PMID:Iron burden and liver fibrosis decrease during a long-term phlebotomy program and iron chelating treatment after bone marrow transplantation. 1654 Apr 26


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