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)

1. With Helix pomatia intracerebral injections of ferritin were carried out (maximal incubation time: 45 min). First, the marker spreads with time via the enxtracellular space throughout the cerebral ganglia and, secondly, is transported out of the ganglia. Electron microscopical studies showed that all glial cell types take up great amounts of ferritin by endocytosis. The plasmatic glial cells at the periphery incorporate more of the marker than the filamentous glial cells in the centre. No uptake of ferritin by neurons or axons was observed. In vitro studies proved that ferritin can penetrate from the connective tissue capsule into the ganglia only after disruption of the neural lamella and damaging of the peripheral glial processes. 2. 3H-glutamate, a putative transmitter of the CNS of Helix pomatia, was injected into the hemocoel of active snails (incubation times: 15 min, 1h, 6h, 3d). Light microscopical evaluation of radioautographs showed that great quantities of the tracer penetrate into the ganglia. The bulk of it is taken up by glial cells, whereas the neurons exhibit only small amounts of the tracer. The studies with ferritin as well as those with 3H-glutamate indicate that the glial cells of the cerebral ganglia of Helix pomatia act as a "hemolymph-neuron barrier". A dominant role of the plasmatic glial cells according to these processes is discussed.
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PMID:The glial cells of the cerebral ganglia of Helix pomatia L. (Gastropoda, Pulmonata). II. Uptake of ferritin and 3H-glutamate. 94 29

Cationic ferritin binds in a time and concentration dependent manner to all surfaces of ciliary ganglion neurons in culture except "mounds" and "veils". In chase experiments, bound ferritin clears from the cells surfaces and forms larger and larger patches, even at low temperatures. Binding of cationic ferritin is inhibited by poly-L-lysine, potentiated by poly-L-glutamate, and not affected by neruaminidase (acylneuraminyl hydrolase, EC 3.2.1.18), hyaluronidase (hyaluronoglucosidase, hyaluronate 4-glycanhydrolase, EC 3.2.1.35), or chondroitin ABC lyase (EC 4.2.2.4).
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PMID:Differential labeling of the cell surface of single ciliary ganglion neurons in vitro. 106 97

Effects of endurance training on O2 transport and on iron status are well documented in the literature. Only a few data are available concerning the consequences of strenuous anaerobic muscular exercise on red cell function. This study was performed to test the influence of strength training alone on parameters of red cell O2 transport and iron status. Twelve healthy untrained males participated in a strength-training programme of 2-h sessions four times a week lasting 6 weeks. After 6 weeks a small but significant reduction of haemoglobin (Hb; -5.4 g.l-1) was found (p less than 0.05). Mean red cell volume did not change, but a pronounced decrease of mean cell Hb concentration (from 329.2 g.l-1, SE 2.5 to 309.8 g.l-1, SE 1.2; p less than 0.001) and mean corpuscular Hb (from 29.6 pg, SE 0.4 to 27.7 pg, SE 0.3; p less than 0.01) was observed. Serum ferritin decreased significantly by 35% (p less than 0.01); transferrin, serum iron and iron saturation of transferrin were unaltered. Serum haptoglobin concentration was diminished significantly by 30.5% (p less than 0.01). The reticulocyte count had already increased after 3 weeks of training (p less than 0.05) and remained elevated during the following weeks. Strength training had no significant influence on the O2 partial pressure at which Hb under standard conditions was 50% saturated, red cell 2,3-diphosphoglycerate and ATP concentration as well as on erythrocytic glutamate-oxalacetate transaminase activity. The data demonstrate that mechanical stress of red cells due to the activation of large muscle masses led to increased intravascular haemolysis, accompanied by a slightly elevated erythropoiesis, which had no detectable influence on Hb-O2 affinity. Training caused an initial depletion of body iron stores (prelatent iron deficiency). Although Hb had decreased by the end of the training phase a true "sports anaemia" could not be detected.
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PMID:Consequences of 6 weeks of strength training on red cell O2 transport and iron status. 234 15

A four-fold (P less than 0.001) mean increase in iron levels was found in 18 patients (a total of 36 courses of therapy) with ovarian cancer at the end of a 5-day course of cisplatin (40 mg/m2 per day every 4-5 weeks). The kinetics of these modifications began very early (24-48 h after initiation of therapy): they reached their maximum on the 4th-5th day, coinciding with the last drug administration, and basal levels were recovered after the 10th day. A subsequent eight-fold average increase (P less than 0.001) in ferritin serum levels, beginning 2 days after the iron changes, was observed, but showed a slower regression (after the 15th day). Reticulocyte counts were lowered (P less than 0.001) with the same time-course of the iron increases, but returned to pretreatment levels within 2 weeks. Total bilirubin and serum glutamate-pyruvate transaminase showed significantly delayed increases compared with iron. The results are in keeping with a reduced iron utilization by the erythroid precursors, but other mechanisms cannot be excluded. There is no statistical correlation between the early iron increases and the subsequent hemoglobin nadir values.
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PMID:Changes in serum iron levels following very high-dose cisplatin. 358 20

We examined the effects of chronic dietary iron overload on hepatic mitochondrial oxidative metabolism. Experimental iron overload was produced by feeding rats a chow diet supplemented with carbonyl iron over a 7-week period. Biochemical and histologic evaluations of liver tissue confirmed moderate degrees of hepatic parenchymal iron overload. Electron microscopy showed no abnormalities in hepatic mitochondrial ultrastructure in blocks of tissue or in mitochondrial fractions from iron-loaded liver. Studies of mitochondrial oxidative metabolism revealed a consistent and progressive decrease in state 3 (ADP-stimulated) respiration and in respiratory control ratios at hepatic iron concentrations above 1,000 micrograms per gm for all three substrates studied, glutamate, beta-hydroxybutyrate and succinate. Changes in state 4 (ADP-limited) respiration and ADP/O ratios were not progressive with increasing hepatic iron concentrations. At hepatic iron concentrations at which there were decreases in state 3 respiration and respiratory control ratios, there was also evidence of lipid-conjugated diene formation, indicative of mitochondrial lipid peroxidation. There were no changes in mitochondrial function when iron as either ferritin or hemosiderin or as a combination of ferritin, hemosiderin and ferric nitrilotriacetate was added in vitro to normal liver homogenates. Use of density gradient centrifugation to reduce iron and lysosomal contamination of mitochondrial fractions failed to prevent the reduction in mitochondrial function. We conclude that moderate degrees of chronic hepatic iron overload in vivo result in an inhibitory defect in the mitochondrial electron transport chain as evidenced by a decrease in state 3 respiration and respiratory control ratios.
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PMID:Hepatic mitochondrial oxidative metabolism in rats with chronic dietary iron overload. 402 91

This study was undertaken to characterize the nitric oxide complexes of mammalian ferritin and their EPR properties to gain a better understanding of the interaction of NO with non-heme iron proteins within the cell. Measurements were made with horse spleen apo- and holoferritins, with chemically modified proteins, and with recombinant human H-chain apoferritin and its site-directed mutants. Three types of EPR signals (A, B, and C) have been identified and attributed to iron-nitrosyl complexes at imidazole groups of histidine, thiol groups of cysteine, and carboxylate groups of aspartate and glutamate, respectively. The C-type axial spectrum has features at g perpendicular' = 4 and g parallel' = 2 characteristic of a paramagnetic Fe(3+)-NO- complex with total spin S = 3/2 and probably arises from nonspecific binding to carboxylate groups on the protein. The S = 1/2 axial B-type signal g perpendicular' = 2.033 and g parallel' = 2.014) is formed at Cys-130 (human H-chain sequence numbering). His-128 and possibly His-118 are sites of formation of the rhombic S = 1/2 A-type complex (gx' = 2.055, gy' = 2.033, and gz' = 2.015); the former residue perhaps plays a role in the conformational stability of the protein as well as in iron binding. The data reveal that the residues Cys-130 and His-128 in the vicinity of 3-fold channels leading to the interior of the protein shell are important in iron-nitrosyl complex formation in mammalian ferritins.
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PMID:Identification of the EPR-active iron-nitrosyl complexes in mammalian ferritins. 814 66

Ferritins are a class of iron storage and mineralization proteins found throughout the animal, plant, and microbial kingdoms. Iron is stored within the protein shell of ferritin as a hydrous ferric oxide nanoparticle with a structure similar to that of the mineral "ferrihydrite." The eight hydrophilic channels that traverse the protein shell are thought to be the primary avenues by which iron gains entry to the interior of eukaryotic ferritins. Twenty-four subunits constitute the protein shell and, in mammalian ferritins, are of two types, H and L, which have complementary functions in iron uptake. The H chain contains a dinuclear ferroxidase site that is located within the four-helix bundle of the subunit; it catalyzes the oxidation of ferrous iron by O(2), producing H(2)O(2). The L subunit lacks this site but contains additional glutamate residues on the interior surface of the protein shell which produce a microenvironment that facilitates mineralization and the turnover of iron(III) at the H subunit ferroxidase site. Recent spectroscopic studies have shown that a di-Fe(III) peroxo intermediate is produced at the ferroxidase site followed by formation of a mu-oxobridged dimer, which then fragments and migrates to the nucleation sites to form incipient mineral core species. Once sufficient core has developed, iron oxidation and mineralization occur primarily on the surface of the growing crystallite, thus minimizing the production of potentially harmful H(2)O(2).
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PMID:Mineralization in ferritin: an efficient means of iron storage. 1044 28

The high-resolution structure of the non-haem ferritin from Escherichia coli (EcFtnA) is presented together with those of its Fe(3+) and Zn(2+) derivatives, this being the first high-resolution X-ray analysis of the iron centres in any ferritin. The binding of both metals is accompanied by small changes in the amino acid ligand positions. Mean Fe(A)(3+)-Fe(B)(3+) and Zn(A)(2+)-Zn(B)(2+) distances are 3.24 A and 3.43 A, respectively. In both derivatives, metal ions at sites A and B are bridged by a glutamate side-chain (Glu50) in a syn-syn conformation. The Fe(3+) derivative alone shows a third metal site (Fe( C)( 3+)) joined to Fe(B)(3+) by a long anti-anti bidentate bridge through Glu130 (mean Fe(B)(3+)-Fe(C)(3+) distance 5.79 A). The third metal site is unique to the non-haem bacterial ferritins. The dinuclear site lies at the inner end of a hydrophobic channel connecting it to the outside surface of the protein shell, which may provide access for dioxygen and possibly for metal ions shielded by water. Models representing the possible binding mode of dioxygen to the dinuclear Fe(3+) pair suggest that a gauche micro-1,2 mode may be preferred stereochemically. Like those of other ferritins, the 24 subunits of EcFtnA are folded as four-helix bundles that assemble into hollow shells and both metals bind at dinuclear centres in the middle of the bundles. The structural similarity of EcFtnA to the human H chain ferritin (HuHF) is remarkable (r.m.s. deviation of main-chain atoms 0.66 A) given the low amino acid sequence identity (22 %). Many of the conserved residues are clustered at the dinuclear centre but there is very little conservation of residues making inter-subunit interactions.
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PMID:The high-resolution X-ray crystallographic structure of the ferritin (EcFtnA) of Escherichia coli; comparison with human H ferritin (HuHF) and the structures of the Fe(3+) and Zn(2+) derivatives. 1125 84

The first ferritin structure refined at the atomic level has been achieved on recombinant mouse L-chain apoferritin (rMoLF) crystals. These latter diffract to 1.2 A resolution under cryogenic conditions. When cryo-cooling the sample, the thermal disorder usually observed at room temperature is reduced and the low-temperature structure reveals several details concerning the protein putative active sites and their properties. Within the pores built up by the molecular three-fold symmetry axes, the iron entry route to the ferritin cavity, residues H118, D131 and E134, exhibit alternate conformations associated with the binding of partially hydrated cadmium ions, a metal used as a crystallization agent. At the mineral ferrihydrite nucleation center, the electron density maps evidence the orientation of E57, E60, E61 and E64 glutamate side chains (whereas they were observed highly disordered in previous ferritin structures determined at room temperature) and allow a description of the site taking into account the binding geometry of four Cd(2+) ions. Moreover, the side chain of residue K140, lying in the vicinity of the ferrihydrite nucleation center, is shown to interact with residue E61. As previously highlighted, this observation confirms the importance of K140 in the rMoLF sequence, as being responsible for the low level of iron incorporation by mousel L-chain ferritin compared to human L-chain ferritin. Finally, the diffusion of small molecules within the ferritin cavity is illustrated here by the presence of ordered molecules of glycerol used as a cryo-protectant, which bind the inner cavity surface of the protein.
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PMID:Structural description of the active sites of mouse L-chain ferritin at 1.2 A resolution. 1245 4

The influence of iron deposits on T2 values and the content of metabolites in the brain of three patients with DNA proved pantothenate kinase-associated neurodegeneration (PKAN, formerly Hallervorden-Spatz syndrome) was studied. An eye-of-the-tiger sign, a typical MR finding for PKAN, was observed in two patients with the same mutation. A hypointensive lesion in a whole globus pallidus was observed in the third patient with the additional mutation. T2 values in the globus pallidus of the patients were about 40% shorter than in controls (71/48 ms in controls vs. patients), which corresponds to the increase of Fe concentration based on the ferritin basis from 17 mg for controls to 48 mg (100 g wet brain weight) in PKAN patients. 1H MR spectroscopy (MRS) has mainly been used to describe neuronal damage represented by decreased NAA (6.4 mmol vs. 9 mmol) and Cr/PCr (7.0 mmol vs. 9.8 mmol) concentrations in the basal ganglia region of the patient group to controls; MRS is much more case-sensitive and describes individual development of the disease as demonstrated in the difference between the spectra of typical PKAN patients (1, 2), and the patient (3) with atypical PKAN development. Any significant changes of metabolite concentration with the exception glutamine, glutamate and GABA were found in the white matter.
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PMID:MR relaxometry and 1H MR spectroscopy for the determination of iron and metabolite concentrations in PKAN patients. 1556 11


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