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

The ultrastructural localization of three cytoskeletal proteins, alpha-actinin, tropomyosin, and vinculin, in the brush border of epithelial cells of chicken small intestine and the smooth muscle cells of chicken gizzard was studied by immunofluorescence and immunonelectron microscope labeling of frozen sections of lightly fixed, intact tissues. In the immunoelectron microscope studies, a recently described new type of electron-dense antibody conjugate, imposil-antibody, has been successfully used, along with ferritin-antibody conjugates, in single and double immunolabeling experiments. In the intestinal brush border shows that vinvulin is sharply confined to the junctional complex close to the membrane region of the zonula adherens, in distinct contrast to the more diffuse distributions of the other two proteins. In the smooth muscle cells, the labeling patterns show that vinculin is sharply confined to the membrane-associated dense plaques, closer to the membrane than the alpha-Actinin is also present in the cytoplastic dense bodies, from which vinculin is absent. Tropomyosin is present diffusely distributed in the cytoplasm, but absent from both dense plaques and dense bodies. These findings with the muscle cells demonstrate, therefore, that the dense plaques and dense bodies are chemically and structurally distinct entities. The results with both tissues, along with those in previous papers (Geiger, 1979, Cell. 18:193-205.; Geiger et al., 1980, Proc. Natl. Acad. Sci. U. S. A. 77:4127-4131), suggest that vinculin may play an important and widespread role in the linkage of actin-containing microfilament bundles to membranes.
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PMID:Immunoelectron microscope studies of membrane-microfilament interactions: distributions of alpha-actinin, tropomyosin, and vinculin in intestinal epithelial brush border and chicken gizzard smooth muscle cells. 679 20

A mechanism is proposed by which apotransferrin is secreted from mucosal cells, loaded with iron in the intestinal lumen, and then the intact complex is taken into the cell. Within the cell, iron is released and transferred to the blood stream, whereas iron-free transferrin returns to the brush border to be recycled. We have investigated this hypothesis by measuring intestinal absorption of radioiron and 125I-labeled plasma transferrin using tied-off gut segments in normal and iron-deficient rats. There was no absorption of diferric transferrin from the ileum, but high absorption from the duodenum and jejunum segments. Jejunal absorption occurred as a function of the dose offered and showed saturation kinetics. In normal animals, 4 micrograms of the 50 micrograms of transferrin iron was absorbed over 1 hr. In iron-deficient animals, mean values as high as 13 micrograms were observed. Radioiron content of the jejunal mucosa bore a linear relationship to the dose administered and was inversely proportional to the amount of iron entering the plasma. Recycling of transferrin was indicated by the presence of labeled apotransferrin in the lumen, first observed between 15 and 60 min after the injection of diferric transferrin. A high resistance of diferric and apotransferrin to proteolytic degradation within the gut lumen was demonstrated. Comparative studies with lactoferrin and ferritin disclosed poor availability of their iron for absorption. The small amount that was absorbed did not relate to the iron status of the recipient animal. These studies support the role of mucosal transferrin as a shuttle protein for iron absorption.
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PMID:The significance of transferrin for intestinal iron absorption. 682 98

A membrane-associated iron-binding complex was isolated from rat intestinal mucosa during iron absorption. Two 59Fe peaks (peaks 1 and 2) were separated on Sepharose 6B gel filtration from detergent solubilized 20,000 x g precipitate of upper intestinal mucosal homogenate after administration of 59Fe-labelled ferrous materials. Peak 1 was a membrane iron-binding complex whose apparent molecular weight was over 10(6) Da estimated by gel filtration, while peak 2 was identified as ferritin. Three major bands were detected on SDS-polyacrylamide gel electrophoresis (SDS-PAGE) of peak 1. The treatment of mucosal homogenate with 5 mM ethylenediaminetetraacetic acid released 59Fe binding from peak 1. Incorporation of 59Fe to peak 1 showed the maximum at 1 h and then reduced, while [59Fe]ferritin showed reciprocal behavior, which suggested that peak 1 may be a rapid turnover iron pool and transfer 59Fe to ferritin. Peak 1 was also isolated from the brush border membrane and showed similar SDS-PAGE pattern to that from the 20,000 x g precipitate of mucosal homogenate. Western blot analysis did not reveal immunoreactive transferrin in peak 1. Those findings suggest that peak 1 may be a non-ferritin, non-transferrin iron-binding complex located on the brush border membrane and accept iron from the intestinal canal during iron absorption.
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PMID:The role of membrane-associated iron-binding complex in intestinal iron absorption in the rat. 775 70

The present study provides at least partly answers to some of the questions outlined in the introduction (see also Figs. 2 and 3): Endocytosis and intracellular transport of ferritin, HRP and insulin tracers (125I-insulin, native insulin and insulin-gold) was followed by use of EM-autoradiography, immunocytochemistry and cytochemistry. Proteins are internalized into endocytic vacuoles and transferred to the lysosomes for degradation. Tracers were not transferred to the Golgi apparatus. 125I-insulin is internalized by specific receptor mediated endocytosis from the apical plasma membrane, substantiating the hypothesis that specific endocytosis receptors are responsible for reabsorption of certain proteins. The binding sites are localized in endocytic invaginations and in the microvillus membrane. The binding sites in the invaginations are responsible for endocytosis, whereas the function of the microvilli binding sites is unclear, but they possess the ability to migrate in the plane of the microvillus membrane. Binding to specific binding sites and subsequent internalization of insulin takes place with high efficiency corresponding to more than 50% of the perfused load. Not all proteins are reabsorbed with high efficiency e.g. EGF which has similar molecular weight and pI is shown to be reabsorbed with substantially lower efficiency (about 4%). Binding and absorption efficiency of insulin may also change due to alterations in flow rate and perfused loads of protein: The load determines the magnitude of uptake and the flow rate determines the efficiency in binding and uptake. These changes are suggested to be caused by concomitant changes in the mean luminal concentration. The reabsorption process for insulin is efficient and of large capacity, and is only saturable (Michaelis-Menten kinetics) at very high concentrations of insulin. The proximal tubular internalization and degradation of 125I-insulin reach steady state rapidly. The processing can be described by a two-compartment model with t1/2 for transfer of 125I-insulin to lysosomes of 8.5 min and for lysosomal degradation of 72 min. 125I-PYY a linear peptide with similar molecular weight as EGF and insulin is not endocytosed but extracted with high efficiency (75% removed) by degradation by brush border peptidases and a substantial transtubular transport of TCA-precipitable PYY takes place by a paracellular route. A small vesicular transport of colloidal tracers was demonstrated constituting about 0.5% of the endocytosed amount. A method for covalently cross-linking insulin tracers to apical binding sites is described and evaluated. Recycling of apical binding sites was estimated to be very efficient and did not involve lysosomes or the Golgi apparatus.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Endocytosis in renal proximal tubules. Experimental electron microscopical studies of protein absorption and membrane traffic in isolated, in vitro perfused proximal tubules. 792 57

The extent of iron deposition in the placenta during the various stages of pregnancy, as well as its significance, has not been clearly established. There often is confusion with regard to calcium deposits. To address this issue 82 placentas (60 from normal pregnancies and 22 from abnormal pregnancies) were examined by light microscopy, including iron and calcium stains, and immunoperoxidase stains for ferritin. Seven cases also were studied ultrastructurally, including x-ray microanalysis. With these modalities we could unequivocally differentiate between iron and calcium deposits. It was concluded that in normal pregnancies the placenta stores iron mainly in two forms: first, at least as soon as the seventh week of gestation Hofbauer cells and the syncytiotrophoblast contain ferritin, which is particularly prominent in the syncytiotrophoblast's brush border; and second, during the first two trimesters of gestation iron also is present as linear granular deposits in the trophoblastic basement membrane. In the presence of anomalies in fetal development the iron deposition in the form of linear granular deposits is markedly increased to a statistically significant degree during the second and third trimesters of pregnancy. It is concluded that granular iron deposits in the trophoblastic basement membrane are normally present, gradually decreasing in the progress of normal pregnancies. Their presence in excess (> 7.5% of villi), however, is a pathologic finding associated with fetal growth anomalies.
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PMID:Placental iron deposits: significance in normal and abnormal pregnancies. 816 71

Using a subtractive hybridization method, we have cloned cDNAs corresponding to 10 different mRNAs which share the property of being expressed in the intestine of adult but not baby rabbits. Four could be identified as coding for previously known gene products (sucrase-isomaltase, a glutathione S-transferase, a cytochrome P450, and a long form of ferritin mRNA), while six code for previously unknown proteins. One clone, AdRab-B, codes for a protein of 1458 amino acids, including (i) a putative signal sequence at the NH2 terminus, (ii) four internal repeats, 308-346 amino acids in length, (iii) a hydrophobic stretch near the COOH terminus, which represents a potential membrane anchor, and (iv) a short hydrophilic stretch at the very COOH terminus. The corresponding protein was studied with the aid of antibodies prepared against polypeptides expressed from segments of the cDNA in Escherichia coli. The protein was shown to be proteolytically processed in the intestine (but not when expressed in COS cells) and to be targeted to the brush border membrane of the enterocytes. Finally, the protein was found to have esterase and phospholipase A/lysophospholipase activity.
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PMID:Messenger RNAs expressed in intestine of adult but not baby rabbits. Isolation of cognate cDNAs and characterization of a novel brush border protein with esterase and phospholipase activity. 850 24

Hephaestin is a membrane-bound multicopper ferroxidase necessary for iron egress from intestinal enterocytes into the circulation. Mice with sex-linked anemia (sla) have a mutant form of Hephaestin and a defect in intestinal basolateral iron transport, which results in iron deficiency and anemia. Ireg1 (SLC11A3, also known as Ferroportin1 or Mtp1) is the putative intestinal basolateral iron transporter. We compared iron levels and expression of genes involved in iron uptake and storage in sla mice and C57BL/6J mice fed iron-deficient, iron-overload, or control diets. Both iron-deficient wild-type mice and sla mice showed increased expression of Heph and Ireg1 mRNA, compared to controls, whereas only iron-deficient wild-type mice had increased expression of the brush border transporter Dmt1. Unlike iron-deficient mice, sla mouse enterocytes accumulated nonheme iron and ferritin. These results indicate that Dmt1 can be modulated by the enterocyte iron level, whereas Hephaestin and Ireg1 expression respond to systemic rather than local signals of iron status. Thus, the basolateral transport step appears to be the primary site at which the small intestine responds to alterations in body iron requirements.
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PMID:Systemic regulation of Hephaestin and Ireg1 revealed in studies of genetic and nutritional iron deficiency. 1273 Jan 11

The formation of protein absorption droplets in the cells of the proximal convolution was studied in mouse kidney. Ox hemoglobin was administered intraperitoneally and kidney specimens were collected at intervals of 30 minutes to 4 days after injection. In the lumen of the nephron, hemoglobin was concentrated to an opaque mass whose relations with the brush border and the epithelium could be easily followed. It was found that hemoglobin passes through the brush border in between the microvilli, enters the channels of tubular invaginations at the bases of the brush border, and is transported in bulk into vacuoles in the intermediate cell zone. These vacuoles increase in size and are transformed through further concentration into dense absorption droplets. Using the opaque hemoglobin content of the nephron as a tracer, functional continuity of the system of the tubular invaginations with the lumen on one side and the vacuoles on the other was demonstrated. Mitochondria lie closely apposed to vacuoles and droplets, but are not primarily involved in droplet formation. 15 hours after injection and later, ferritin and systems of layered membranes become visible in the droplets as their density decreases. These membranes are interpreted as lipoprotein membranes; similar membranes are found in the lumen of the tubuli. It is suggested that phospholipids enter into the vacuoles together with hemoglobin from the tubular lumen and form membrane systems of lipoproteins in the droplets. At 3 to 4 days the droplets contain aggregates of ferritin, and the iron reaction becomes positive in the tubule cells. No significant changes were found in the Golgi apparatus or in the microbodies during hemoglobin absorption. At all time points investigated, the terminal bars seal the intercellular spaces against penetration by hemoglobin in the proximal and distal convolutions and in the collecting ducts.
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PMID:Hemoglobin absorption by the cells of the proximal convoluted tubule in mouse kidney. 1377 Jul 60

Renal Fanconi syndrome developed rapidly in a 3-year-old Moroccan girl with established lysinuric protein intolerance. She was hospitalized because of lowered consciousness, uncoordinated movements and hepatosplenomegaly after a febrile period. Laboratory investigations revealed plasma ammonia 270 micromol/L (normal <70 micromol/L), ferritin 159 micromol/L (normal 2-59 micromol/L), LDH 1180 U/L (normal 26-534 U/L). LPI was diagnosed based on the findings of reduced plasma ornithine, arginine and lysine, and an increased level of glutamine. Urinary orotic acid (645 micromol/mmol creatinine; normal <3.6) was strongly increased. A defect in the SLC7A7 amino acid transporter was established (homozygous c.726G > A mutation). Detailed renal function tests including an acid challenge test, bicarbonate loading, and tubular maximal reabsorption of glucose showed complex tubular dysfunction. No evidence of respiratory chain defects was found in muscle or kidney tissue. No morphological abnormalities were demonstrated in the mitochondria. Ultrastructural analysis of proximal tubular cells showed vacuolization and sloughing of the apical brush border (Fig. 1). Renal involvement in LPI has only been described in a few reports; however, no detailed studies of the renal acidification mechanism were performed. Our patient had evidence of a full-blown Fanconi syndrome. Surprisingly, a metabolic acidosis was found with a moderately increased serum anion gap combined with repeatedly normal plasma organic acid values. This finding is in contrast with the diagnosis of renal tubular acidosis. Patients with hyperlysinaemia have a similar heavy load on the renal tubules; they never develop a renal Fanconi syndrome. Therefore, we consider the intratubular accumulation of lysine an unlikely candidate for the development of the renal Fanconi syndrome.
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PMID:Renal Fanconi syndrome with ultrastructural defects in lysinuric protein intolerance. 1753 Apr 37

The human intestinal epithelium is composed of several cell types, mainly enterocytes and goblet (mucin-secreting) cells. This study compares the cellular response of Fe transporters in Caco-2, HT29-MTX, and Caco-2/HT29-MTX co-culture models for Fe bioavailability. Caco-2 cells in vitro differentiate into enterocyte-like cells and HT29-MTX cell lineage into a mucin-secreting cellular population. Cell cultures were exposed to digests of Fe+3, Fe+3/ascorbic acid, cooked fish (high-available Fe) or white beans (low-available Fe). Cell responses as shown by mRNA expression of the main Fe transporters, DMT1 and DcytB, and cell ferritin formation were monitored. In Caco-2/HT29-MTX co-cultures, the mucin layer lowered the pool of free Fe to diffuse towards the cell brush border membrane of enterocytes, which was accompanied of an upregulation of DMT1 mRNA expression. In contrast, cultures exposed to digests of fish or white beans showed no significant differences in the regulation of Fe transporters.
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PMID:Different responses of Fe transporters in Caco-2/HT29-MTX cocultures than in independent Caco-2 cell cultures. 1952 86


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