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)

Metabolic balance for lead and cadmium were carried out in 23 healthy elderly people aged 69.7 to 85.5 yr while living in their own homes and eating self-selected diets. Mean intakes of lead and cadmium were 54.6 and 8.6 micrograms/day, with mean retentions of -8.7 and -1.7 micrograms/day, respectively. Daily dietary lead correlated (p less than 0.05) with the intake of energy, nitrogen, calcium, iron, and zinc but not with manganese or copper. Dietary intake of cadmium correlated (p less than 0.05) only with that of zinc and manganese. There was a highly significant (p less than 0.001) inverse correlation between the percentage cadmium absorbed and body iron stores measured as serum iron, percentage iron saturation, and ferritin. Mean whole blood concentrations were 138 micrograms/l for lead and 0.79 microgram/l for cadmium. The negative balances observed in these elderly people were very different from the positive balances found in a previous similar study in children.
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PMID:The intake and excretion of lead and cadmium by the elderly. 671 83

Non-transferrin-bound iron (NTBI) plays an important role in the hepatocellular injury induced by iron overload. However, the mechanism responsible for NTBI uptake into hepatocytes remains poorly defined. The purpose of this study was to define the kinetics of NTBI uptake by isolated rat hepatocytes and to characterize the uptake process. NTBI uptake was time and temperature dependent, exhibited a Michaelis-Menten constant (Km) value of 1.25 microM and maximum uptake of 241 pmol.10(6) cells-1.min-1, and 55Fe was incorporated in part into intracellular ferritin. Uptake was Ca2+ dependent, exhibiting 15 and 80% of maximal uptake in the presence of 0.6 and 0.75 mM CaCl2, respectively. The putative NTBI transporter was highly specific; divalent (Zn2+, Mn2+, Cd2+, and Co2+) or trivalent (La3+) cations did not inhibit Fe3+ uptake. Reduction from Fe3+ to Fe2+ was not essential for uptake or the process occurred deep within the membrane bilayer, since the Fe2+ chelator ferrozine did not influence 55Fe uptake. These data provide evidence for a low Km plasma membrane transporter for NTBI, which should be functional at physiological serum concentrations and saturated in iron-overload diseases, such as hemochromatosis.
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PMID:Evidence for a low Km transporter for non-transferrin-bound iron in isolated rat hepatocytes. 748 9

The formation of Mn(III) oxyhydroxide (MnOOH) cores within the nanoscale cavity of the iron storage protein ferritin has been investigated by electron microscopy and visible absorption spectroscopy. At pH 8.9, discrete amorphous MnOOH cores were formed within horse spleen apoferritin at a range of metal:protein ratios, as well as in ferritin molecules seeded with a small ferrihydrite nucleus. Analysis of the resultant core size distributions showed that the reconstitution of horse spleen apoferritin with Mn(II) was similar to that observed previously for Fe(II) reconstitution in recombinant human L-chain ferritin, suggesting that horse spleen apoferritin does not exhibit Mn(II) oxidase activity at pH 8.9. Reconstitution with MnOOH shows essentially "all-or-nothing" behavior in which many protein molecules remain unmineralized whilst others are loaded to maximum capacity. Kinetic studies showed no significant differences between horse spleen ferritin, recombinant H- and L-chain homopolymers, and H-chain variants containing site-directed modifications at the ferroxidase and putative Fe nucleation centers. Our results indicate that the reconstitution of ferritin with MnOOH cores proceeds by a nonspecific pathway. We propose that the outer surface of the protein inhibits the development of MnOOH nuclei in bulk solution whereas the inner surface is inactive, enabling nucleation and growth to proceed unperturbed within the cavity. One possibility is that differences in the general polyelectrolyte properties of these two surfaces, rather than site-specific charges, account for the "Janus" behavior of the molecule. A similar mechanism might also increase the specificity of iron oxide mineralization in ferritins that lack ferroxidase centers.
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PMID:Reconstitution of manganese oxide cores in horse spleen and recombinant ferritins. 773 39

The binding of Cd2+, Zn2+, Cu2+, Ni2+, Co2+, Mn2+, and Mg2+ to apo, holo, reconstituted horse spleen ferritin (HoSF), and native holo HoSF with phosphate removed was measured by gel-exclusion chromatography. Three classes of strong binding interactions (Kd < 10(-7) M) with apo HoSF at pH 7.5 were found for the various M2+ studied: high stoichiometric binding (30-54 M2+/HoSF) for Cd2+, Zn2+, Cu2+, with two protons released per metal bound; intermediate binding (16 M2+/HoSF) for Ni2+ and Co2+, with one proton released per metal bound; and low levels of binding (2-12 M2+/HoSF) for Mn2+, Mg2+, and Fe2+, with < 0.5 protons released per metal bound. M2+ binding to apo HoSF was nearly abolished at pH 5.5, except for Fe2+ and Cu2+, which remained unaffected by pH alteration. Holo HoSF bound much higher levels of M2+, a result directly attributable to the presence of phosphate binding sites. This conclusion was confirmed by decreased binding of M2+ to HoSF reconstituted in the absence of phosphate and by native holo HoSF with phosphate chemically removed. The binding of Cd2+ to apo HoSF was 54 per HoSF, but in the presence of developing core, the amount bound decreased to about 30 Cd2+/HoSF. This result indicated that Cd2+ and developing core were competing for the same sites on the HoSF interior, suggesting that 24 of the Cd2+ were bound to the inside surface. No other M2+ studied bound to the interior of HoSF by this criterion. Several of the M2+ appeared to bind strongly to the phosphate-free mineral core surface in reconstituted HoSF.
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PMID:Metal ion binding to apo, holo, and reconstituted horse spleen ferritin. 778 91

The present study provides evidence for anterograde axonal transport of manganese (Mn) in the basal ganglia. Microinjections of 54Mn into rat substantia nigra or striatum revealed region-specific accumulation and retention of the isotope in globus pallidus, striatum, thalamus and substantia nigra for up to at least 48 or 72 h respectively. Within 4 h after intrastriatal injection of 54Mn, radioactivity accumulated in the substantia nigra, suggesting axonal transport of the metal. Subsequent studies using bilateral 54Mn injections into striatum or substantia nigra and unilateral colchicine injections into or transection of the medial forebrain bundle confirmed axonal transport of Mn through these fibres. Selective destruction of the striatonigral or nigrostriatal pathways using quinolinic acid or 6-hydroxydopamine 2 weeks before injection of the isotope, revealed uptake of 54Mn by cell bodies of both gamma-aminobutyric acidergic striatal and dopaminergic nigral neurons and subsequent anterograde transport through striatonigral or nigrostriatal fibres. In addition, the quinolinic acid-lesioned striatum retained three times more radioactivity than the intact striatum. In conclusion, the present data suggest that both glial cells and striatonigral and nigrostriatal neurons are potential targets for Mn toxicity. These results and the selective neurotoxicity of Mn are discussed with respect to the iron transport protein transferrin, transferrin receptors, the iron storage protein ferritin, and mitochondrial dysfunction.
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PMID:Axonal transport of manganese and its relevance to selective neurotoxicity in the rat basal ganglia. 782 Jun 9

Men (n = 20) and women (n = 20) consuming a diet adequate in manganese were fed 0.037 mBq 54Mn in a test meal. Subjects were counted in a whole-body counter for 70 d to determine whole-body retention of 54Mn. Data from days 10 to 20 and from days 19 to 70 were analyzed by linear regression to calculate absorption and biological half-life. Men absorbed significantly less 54Mn than women, but the 54Mn absorbed had a longer half-life in men. Estimates of absorption were higher, and estimates of half-life were lower, when data from days 10 to 20 were used compared with days 19 to 70. There was a significant association between manganese absorption and plasma ferritin concentrations and between manganese absorption and biological half-life. We conclude that men and women differ in manganese metabolism and that such differences may be related to iron status. We also conclude that regression estimates of absorption determined by using whole-body retention curves depend on the portion of the data used.
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PMID:Sex affects manganese absorption and retention by humans from a diet adequate in manganese. 798 39

Ferritin is a 24 subunit protein that controls biomineralization of iron in animals, bacteria, and plants. Rates of mineralization vary among members of the ferritin family, particularly between L and H type subunits of animal ferritins which are differentially expressed in various cell types. To examine ferritin from a highly differentiated cell type and to clarify the relationship between ferritin structure and function, bullfrog red cell L ferritin has been cloned, overexpressed in E. coli, and crystallized under two conditions. Crystals were obtained at high ionic strength in the presence of MnCl2 at a concentration comparable to that of the protein and in the presence of MgCl2 at a concentration much higher than that of the protein. Under both crystallization conditions, the crystals are tetragonal bipyramids in the space group F432 with unit cell dimensions a = b = c = 182 +/- 0.5 A. Crystals obtained in the presence of manganese and ammonium sulfate diffract to 1.9 A, while those obtained in the presence of magnesium and sodium tartrate diffract to 1.6 A. Isomorphous crystals have been obtained under similar conditions for a site-directed mutant with a reduced mineralization rate in which Glu-57, -58, -59, and -61 are all replaced by Ala. The structure of wild type L-subunit with magnesium has been solved by molecular replacement using the calcium salt of human liver H subunit (Lawson et al., Nature (London) 349:541-544, 1991) as the model. The crystallographic R factor for the 6-2.2 A shell is 0.21. The overall fold of human H and bullfrog L ferritins is similar with an rms difference in backbone atomic positions of 0.97 A. The largest structural differences occur in the D helix and the loop connecting the D and E helices of the four helix bundle. Because red cell L ferritin and liver H ferritin show differences in both rates of mineralization and three-dimensional structure, more detailed comparisons of these structures are likely to shed new light on the relationship between conformation and function.
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PMID:Crystallization and structural analysis of bullfrog red cell L-subunit ferritins. 815 61

Brain tissue from normal individuals with incidental Lewy bodies and cell loss in pigmented substantia nigra neurons (asymptomatic Parkinson's disease) and age-matched control subjects without nigral Lewy bodies was examined biochemically. There was no difference in dopamine levels or dopamine turnover in the caudate and putamen of individuals with incidental Lewy body disease compared to control subjects. There were no differences in levels of iron, copper, manganese, or zinc in the substantia nigra or other brain regions from the individuals with incidental Lewy body disease compared to those from control subjects. Similarly, ferritin levels in the substantia nigra and other brain areas were unaltered. There was no difference in the activity of succinate cytochrome c reductase (complexes II and III) or cytochrome oxidase (complex IV) between incidental Lewy body subjects and control subjects. Rotenone-sensitive NADH coenzyme Q1 reductase activity (complex I) was reduced to levels intermediate between those in control subjects and those in patients with overt Parkinson's disease, but this change did not reach statistical significance. The levels of reduced glutathione in substantia nigra were reduced by 35% in patients with incidental Lewy body disease compared to control subjects. Reduced glutathione levels in other brain regions were unaffected and there were no changes in oxidized glutathione levels in any brain region. Altered iron metabolism is not detectable in the early stages of nigral dopamine cell degeneration. There may be some impairment of mitochondrial complex I activity in the substantia nigra in Parkinson's disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Indices of oxidative stress and mitochondrial function in individuals with incidental Lewy body disease. 828 90

The present study characterizes the transport of nontransferrin (non-Tf) iron by K562 cells. Accumulation of radiolabel by cells incubated with 55Fe-nitrilotriacetate (NTA) is a saturable process that is time and temperature dependent (Ea approximately 20 kcal/mol). Initial rate analysis of iron influx yields values of Vmax = 855 fmol/min/10(6) cells and apparent Km = 0.54 microM. NHCL4 and chloroquine, agents that block cellular acquisition of iron from Tf, do not interfere with assimilation from FeNTA, demonstrating that uptake is truly independent of the Tf-mediated pathway. Furthermore, the inactivation of this transport mechanism by limited proteolytic digestion on ice indicates that specific cell surface proteins are involved. The extent of radiolabel incorporation into heme and ferritin is the same regardless of whether K562 cells acquire iron from 55FeNTA via the cell surface mechanism or from 55Fe-Tf via receptor-mediated endocytosis. Unlike other Tf-independent iron transport pathways that have been described, the K562 cell transport mechanism is not inhibited by divalent cations such as Ni2+, Co2+, or Mn2+. Uptake from 55FeNTA can be blocked by Cu2+ but at concentrations > 1500-fold molar excess. However, Cd2+ is a fairly specific inhibitor of 55Fe uptake by K562 cells (IC50 approximately 50 microM). Additionally, the K562 cell transport mechanism is not Ca2+ dependent and does not appear to be regulated by extracellular iron salts, in contrast to features noted for non-Tf iron uptake by fibroblasts (Sturrock, A., Alexander, J., Lamb, J., Craven, C. M., and Kaplan, J. (1991) J. Biol. Chem. 265, 3139-3145; Kaplan, J., Jordan, I., and Sturrock, A. (1991) J. Biol. Chem. 266, 2997-3004). These unique characteristics of the K562 cell uptake mechanism suggest that multiple transport systems function in Tf-independent iron assimilation.
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PMID:Characterization of transferrin-independent iron transport in K562 cells. Unique properties provide evidence for multiple pathways of iron uptake. 847 96

Exposure to manganese compounds often occurs as the result of industrial production or mining. Although manganese appears in traces in animal and human tissue and is essential to certain biological processes, it is also toxic. In humans and animals, toxicity is mainly associated with the nervous system. The mechanism underlying behavioral and biochemical alterations observed after manganese intoxication is not fully understood. We have shown that the manganese present in serum after exposure to manganese oxide is bound to transferrin as trivalent manganic ion. In this study of manganese uptake and storage we used a clone of human neuroblastoma cells (SHSY5Y). These cells differentiate and express catecholaminergic properties. Saturation binding analysis of the transferrin-manganese complex to the cells revealed a single class of binding sites, with an apparent KD of 13 +/- 1 nM and a density of 11,000 +/- 2,000 binding sites per cell. The complex was internalized in a temperature-dependent way and reached saturation after 2 h when approximately 2% of the added manganese had been internalized. About 80% of the internalized manganese was found in ferritin after 24 h of exposure. The results demonstrate that the transferrin receptor on SHSY5Y cells can bind and internalize a manganese-transferrin complex as efficiently as an iron-transferrin complex, although a saturation of the manganese uptake was achieved.
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PMID:Receptor-mediated endocytosis of a manganese complex of transferrin into neuroblastoma (SHSY5Y) cells in culture. 851 58


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