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

We studied uptake of iron from Fe(III)-diethylenetriamine pentaacetate (DTPA) in isolated rat hepatocytes. This uptake is specific with an affinity of 600 nM and shows an optimum pH of 6. The specificity is indicated by inhibition by ferric citrate and diferric transferrin. Iron uptake from Fe(III)-DTPA is completely inhibited by trypsinization of the cell surface, by strong impermeant ferric chelators (DTPA, apo-transferrin, polymer-conjugated desferrioxamine), both hexacyanoferrates, copper and zinc, and partly by dipyridyl, manganese, cobalt, N-ethylmaleimide, and citrate. The lysosomotropic agent chloroquin inhibits weakly; proton pump inhibitors are without effect. Ascorbate and Tiron both effectively stimulate the uptake and also mobilize iron from DTPA in vitro. Approximately 75% of the freshly acquired intracellular iron is found in ferritin even after uptake at lowered temperature (16 degrees C). We conclude that a rate-limiting mobilization of iron from the DTPA chelate by a cell-surface activity is required before iron can actually enter the cell. This can be enhanced by mediators of iron release, but does not seem to require reduction of iron. The use of DTPA as chelator offers the possibility of studying this putative activity because the Fe(III)-DTPA chelate is stable in the presence of transferrin or desferroxamine, in contrast to ferric citrate or Fe(NTA)2.
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PMID:Uptake of iron by isolated rat hepatocytes from a hydrophilic impermeant ferric chelate, Fe(III)-DTPA. 861 Oct 22

New atherosclerosis causative factors and preventive modalities have been identified. Atherogenic factors include lipid oxidation products, such as cholesterol oxidation products, malonaldehyde and other aldehydes; trans-fatty acids; some saturated fatty acids (lauric, myristic and possibly palmitic acids); and myristic acid plus cholesterol. Lipid oxidation products are well suited to induce arterial damage, based on their known cytotoxic effects; evidence also indicates the possibility of plaque promotion and stimulation of thrombogenesis. Anti-atherogenic factors include antioxidants, fish oils and other polyunsaturates (if protected from oxidation), fibre and trace minerals such as copper, manganese, selenium and zinc. Iron is unique, being considered as both a potential promoter of atherosclerosis (component of ferritin, conceivably inducing lipid oxidation) and a possible anti-atherogenic component (of antioxidant enzyme catalase). It is apparent that an entire new series of research challenges has been uncovered.
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PMID:Atherogenic and anti-atherogenic factors in the human diet. 866 Apr

Blood manganese levels and iron status indices were determined each trimester in 66 healthy pregnant women. Twenty-five were randomly assigned to iron supplementation, 19 to placebo and 22 received dietary advise aimed at increasing their dietary intake of fibre. Iron supplemented women had significantly higher levels of blood haemoglobin compared to the levels of the two other groups, and higher serum ferritin levels compared to the placebo group. No significant difference in blood manganese levels was observed among the three groups of women. There was a significant increase in blood manganese levels from one trimester to the next, which was slightly more pronounced in non supplemented women. The median values in the three trimesters were 154 (range 79-360) nmol/L, 190 (range 98-408) nmol/L, and 230 (range 133-481) nmol/L, respectively. Pregnancy seems to change manganese status or otherwise influence manganese metabolism irrespective of iron status and iron supplementation.
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PMID:Changes in blood manganese levels during pregnancy in iron supplemented and non supplemented women. 884 52

The uptake of 59Fe ascorbate by suspensions of human enterocytes prepared from endoscopically derived duodenal biopsies was studied, with each subject's serum ferritin concentration determined at the time of endoscopy. Iron uptake was greatest at 37 degrees C. Uptake increased from pH 5.5 to 7.3, before being totally inhibited at pH 9.0. However, ferrous ion concentration, determined by 3-(2-Pyridyl)-5,6-bis(4-phenyl sulfonic acid)-1,2,4-triazine, was greatest at pH 5.5 and fell over this pH range. The rate of uptake was significantly greater by enterocytes isolated from individuals with a low serum ferritin (< 22 ng/L) compared with those with normal serum ferritin (> 22 ng/L). Vmax +/- (SEM) was 78.7 +/- 8.5 pmol Fe/(micrograms DNA.min) in the normal group (n = 12) and 141 +/- 17.2 pmol Fe/(micrograms DNA.min) in the low ferritin group (n = 4, P < 0.008). Corresponding Km values were 52.5 +/- 11.7 and 66.7 +/- 5.1 mumol/L, respectively (P < 0.91). Zinc, lead, cobalt and manganese added to the incubation buffer significantly lowered iron uptake into cells (unselected patients). The concentrations of each metal required to halve the uptake rate from 50 mumol/L iron (IC50) were 85 +/- 5 mumol/L (Zn), 570 +/- 170 mumol/L (Pb), 1.1 +/- 0.1 mmol/L (Co), and 3.8 +/- 0.7 mmol/L (Mn). The results demonstrate that enterocytes isolated by this method show the characteristics of iron uptake seen in animal studies. We suggest that these cells will be useful in the study of iron uptake in humans.
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PMID:Iron uptake by isolated human enterocyte suspensions in vitro is dependent on body iron stores and inhibited by other metal cations. 904 May 63

We have synthesized a novel six-coordinate metal chelator from the triamine cis-1,3,5-triaminocyclohexane by the addition of a 2-pyridylmethyl pendant arm on each nitrogen, which we term tachpyr. The experiments described here were designed to explore whether this compound exhibits potential antitumor activity. When added to MBT2 or T24 cultured bladder cancer cells, tachpyr was profoundly cytotoxic, with an IC50 of approximately 4.6 micromol/L compared with 70 micromol/L for desferioxamine. To explore the mode of action of tachpyr, several metal complexes were prepared, including Fe(II), Ca(II), Mn(II), Mg(II), Cu(II), and Zn(II) tachpyr complexes. Of these, the Zn(II), Cu(II), and Fe(II) complexes were without toxic effect, whereas the Ca(II), Mn(II), and Mg(II) complexes remained cytotoxic. To further probe the role of Zn(II) and Cu(II) chelation in the cytotoxicity of tachpyr, sterically hindered tachpyr derivatives were prepared through N-alkylation of tachpyr. These derivatives were unable to strongly bind Fe(III) or Fe(II) but were able to bind Zn(II) and Cu(II). When added to cells, these sterically hindered tachpyr derivatives were nontoxic, consistent with a role of iron depletion in the cytotoxic mechanism of tachpyr. Further, the addition of tachpyr to proliferating cultures resulted in an early and selective inhibition of ferritin synthesis, an iron storage protein whose translation is critically dependent on intracellular iron pools. Taken together, these experiments suggest that tachpyr is a cytotoxic metal chelator that targets intracellular iron, and that the use of tachpyr in cancer therapy deserves further exploration.
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PMID:Tumor cell cytotoxicity of a novel metal chelator. 969 27

The function of the pfr gene encoding the ferritin from Helicobacter pylori was investigated using the Fur titration assay (FURTA) in Escherichia coli, and by characterization of a pfr-deficient mutant strain of H. pylori. Nucleotide sequence analysis revealed that the pfr region is conserved among strains (> 95% nucleotide identity). Two transcriptional start sites, at least one of them preceded by a sigma 70-dependent promoter, were identified. Provision of the H. pylori pfr gene on a multicopy plasmid resulted in reversal of the Fur-mediated repression of the fhuF gene in E. coli, thus enabling the use of the FURTA for cloning of the ferritin gene. Inactivation of the pfr gene, either by insertion of a resistance cassette or by deletion of the up- and downstream segments, abolished this function. Immunoblot analysis with a Pfr-specific antiserum detected the Pfr protein in H. pylori and in E. coli carrying the pfr gene on a plasmid. Pfr-deficient mutants of H. pylori were generated by marker-exchange mutagenesis. These were more susceptible than the parental strain to killing by various metal ions including irons, copper and manganese, whereas conditions of oxidative stress or iron deprivation were not discriminative. Analysis by element-specific electron microscopy revealed that growth of H. pylori in the presence of iron induces the formation of two kinds of cytoplasmic aggregates: large vacuole-like bodies and smaller granules containing iron in association with oxygen or phosphorus. Neither of these structures was detected in the pfr-deficient mutant strain. Furthermore, the ferritin accumulated under iron overload and the pfr-deficient mutant strains lacked expression of a 12 kDa protein which was negatively regulated by iron in the parental strain. The results indicate that the nonhaem-iron ferritin is involved in the formation of iron-containing subcellular structures and contributes to metal resistance of H. pylori. Further evidence for an interaction of ferritin with iron-dependent regulation mechanisms is provided.
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PMID:Structural, functional and mutational analysis of the pfr gene encoding a ferritin from Helicobacter pylori. 978 98

Twenty-seven infants with classical phenylketonuria were evaluated longitudinally for 6 mo while ingesting Phenex-1 Amino Acid Modified Medical Food With Iron as their primary protein source. Intake of selected nutrients and biochemical indices of trace and ultratrace mineral status and plasma retinol and alpha-tocopherol concentrations were evaluated. The means of iron status indices (complete blood count, plasma ferritin, iron, transferrin saturation, total iron binding capacity) and the plasma concentrations of trace and ultratrace minerals (copper, manganese, molybdenum, selenium, zinc) and plasma retinol and alpha-tocopherol were in the reference ranges. Vitamin A intakes (r = 0.49, p < 0.05) and plasma retinol-binding protein concentrations (r = 0.42, p < 0.05) were positively correlated with plasma retinol concentrations at 3 mo of study. At 6 mo, concentrations of plasma transthyretin (r = 0.72, p < 0.01) and retinol-binding protein (r = 0.48, p < 0.05) were positively correlated with plasma retinol concentrations. At 6 mo, concentrations of plasma transthyretin (r = 0.52, p < 0.05) were positively correlated with retinol-binding protein concentrations. Phenex-1 supports normal mean iron status indices and mean concentrations of trace and ultratrace minerals, retinol, and alpha-tocopherol when fed in adequate amounts.
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PMID:Plasma micronutrient concentrations in infants undergoing therapy for phenylketonuria. 1006

The aim of this study was to set up an in vitro model for studying the importance of an altered extra-cellular matrix composition and its importance for the resistance to oxidative stress, in hepatocytes from normal and iron loaded rats. Primary cultures of hepatocytes from iron loaded and normal rats were plated on a laminin rich extracellular matrix or on collagen type I, and incubated with tert-butyl hydroperoxide (TBH). Malon dialdehyde (MDA) and the activities of lactate dehydrogenase (LDH) in cell culture medium were analyzed. The protein synthesis, the concentrations of glutathione and the expression of manganese-superoxide dismutase and ferritin genes were measured. All hepatocytes contained lower concentrations of glutathione when plated on collagen than on EHS. Ferritin H and Mn-SOD gene expression showed no difference. The rate of lipid peroxidation in iron loaded hepatocytes exposed to TBH was higher on collagen than in those plated on EHS (0.95 +/- 0.28 microM MDA vs. 1.62 +/- 0.22 microM MDA, p < 0.05). Iron loaded cells were in general more susceptible to TBH than were normal hepatocytes (MDA, LDH, protein synthesis and glutathione content). Lipid peroxidation could be prevented by adding desferrioxamine. In conclusion, we show that the combination of iron overload and collagen matrix in rat hepatocytes leads to an increased susceptibility to oxidative stress. These findings may be of interest for the further studies on effects of iron overload and the altered matrix composition in liver fibrosis.
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PMID:Susceptibility of cultured rat hepatocytes to oxidative stress by peroxides and iron. The extracellular matrix affects the toxicity of tert-butyl hydroperoxide. 1022 73

Dietary and nutritional status of individuals habitually consuming a vegan diet was evaluated by biochemical, hematologic, and immunologic measures in comparison with a nonvegetarian group. On the basis of 4-d dietary records, the intake of female and male vegans tended to be lower in fat, saturated fat, monounsaturated fat, and cholesterol and higher in dietary fiber than that of vegetarians. With computed food and supplement intakes, vegan diets provided significantly higher amounts of ascorbate, folate, magnesium, copper, and manganese in both female and male participants. The body mass index (BMI; in kg/m(2)) of the vegans was significantly lower than that of the nonvegetarians and 9 of the 25 vegans had a BMI <19. Serum ferritin concentrations were significantly lower in vegan men but iron and zinc status did not differ between the sexes. Mean serum vitamin B-12 and methylmalonic acid concentrations did not differ; however, 10 of the 25 vegans showed a vitamin B-12 deficit manifested by macrocytosis, circulating vitamin B-12 concentrations <150 pmol/L, or serum methylmalonic acid >376 nmol/L. Vegans had significantly lower leukocyte, lymphocyte, and platelet counts and lower concentrations of complement factor 3 and blood urea nitrogen but higher serum albumin concentrations. Vegans did not differ from nonvegetarians in functional immunocompetence assessed as mitogen stimulation or natural killer cell cytotoxic activity.
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PMID:Dietary intake and biochemical, hematologic, and immune status of vegans compared with nonvegetarians. 1047 36

Superoxide anion production in neutrophils plays an important role in the microbicidal defense system in the body. In this study, isolated rat neutrophils were stimulated experimentally and examined by electron microscopy to determine the site of superoxide production and its subsequent translocation during different cell stimulation time periods. Blood and peritoneal neutrophils were incubated for periods of 5, 10, and 15 min with phorbol 12-myristate 13-acetate (PMA), N-formyl-Met-Leu-Phe (fMLP), and combinations of PMA and cytochalasin B (CB) and fMLP and CB. Ultracytochemical detection of O(2)(-) was performed with the 3, 3'-diaminobenzidine-manganese (DAB/Mn) cytochemical method and cationized ferritin (CF) particles were added to stimulation media to monitor endocytotic events that occurred during neutrophil stimulation. Unstimulated neutrophils were devoid of O(2)(-) activity in cytoplasmic granules and at the plasma membrane surface. After 5 min stimulations with PMA, PMA + CB, or fMLP + CB, electron-dense DAB/Mn reaction product was detected in small, centrally located tubular compartments within the neutrophils. CF particles which were added to the stimulation media became internalized in endocytotic vesicles after 5 min stimulation; these vesicles were devoid of O(2)(-) activity. At 10 min stimulation with PMA, O(2)(-)-positive granules subsequently fused with each other and translocated to sub-plasma membrane regions where they either contacted the plasma membrane or fused with CF-containing endocytotic vesicles. Little reaction product was observed on the surface of the neutrophils. Spectrophotometric comparison of the stimulatory effects of PMA, fMLP, and fMLP + CB revealed different rates and yields of O(2)(-) production. Results from this study suggest that the O(2)(-)-producing sites of rat neutrophils originate intracellularly and translocate to the plasma membrane surface following stimulation with PMA, PMA + CB, and fMLP + CB, but not with fMLP or CB alone. Furthermore, these compartments appear to possess the ability to fuse with endocytotic vesicles, a process that may be linked to intracellular microbicidal activity in circulating and tissue neutrophils.
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PMID:Ultracytochemical study on the localization of superoxide producing sites in stimulated rat neutrophils. 1064 63


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