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Results for “Receptors, Transferrin”

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At least 19 recordsLinked to original sources

PubMed1992

The effects of transferrin receptor antibody, transferrin receptor antibody bound to Pseudomonas exotoxin and transforming growth factor-alpha bound to Pseudomonas exotoxin on human tenon's capsule fibroblast proliferation.

Pharmacological agents which modulate the wound healing process by the inhibition of proliferation of fibroblasts may improve the success of glaucoma filtration surgery. Since cell proliferation is essential to the wound healing process, we targeted the surface receptors that are associated with proliferating cells. We present the effects of three such agents-purified mouse anti-human transferrin receptor monoclonal antibody 42/6 (anti-TfR-42/6), anti-transferrin monoclonal antibody bound to a Pseudomonas exotoxin (anti-TfR-PE40) and transforming growth factor-alpha Pseudomonas exotoxin (TGF-alpha-PE40)--on human fibroblasts from Tenon's capsule. The inhibition of human subconjunctival fibroblast proliferation by anti-TfR-42/6 (with a concentration up to 25 micrograms/ml) and by anti-TfR-PE40 and TGF-alpha-PE40 (both with a concentration range of 5000-0.00001 micrograms/ml) was determined by colorimetric (OD), and cell counting (CC) assays over a 9-day period. Neither anti-TfR-42/6 nor anti-TfR-PE40 had an antiproliferative effect on the fibroblasts. TGF-alpha-PE40 demonstrated an antiproliferative effect in a dose response manner. The mean 50% inhibitory dose (ID50) by OD was 32.91 micrograms/ml, while the ID50 by CC was 27.88 micrograms/ml. EGF was used as a negative control for TGF-alpha-PE40 toxin. The inhibitory effect of the toxin conjugate was completely blocked by the addition of 1000 micrograms/ml of EGF. These in vitro studies show that TGF-alpha-PE40 may be useful in modulating the proliferation of human ocular fibroblasts; they also give some indication of drug dosages for future in vivo testing.

ADP Ribose Transferases↗

PubMed1992

[Study on cell proliferation of oral malignant tumor with transferrin receptor].

Transferrin receptor (TfR) is found in the vigorous proliferating cells. The author performed an immunohistochemical study on the TfR expression in the oral tissues and a flow cytometric analysis of TfR in the Hela cells with and without an anticancer drug (CDDP). Immunohistochemically a strong reaction of the TfR was clearly found in the basal and parabasal layers of the normal epithelium and malignant tumors but rarely found in the benign tumors. In the well differentiated carcinomas, the degree of staining was not so high as compared with the poorly differentiated ones. The fluorescence intensity of the cells in the CDDP 0.5 micrograms/ml group was not different from that in the control group. The intensity in the 1.0 micrograms/ml, 24 hr group was almost the same as that in the control group, but in the 1.0 micrograms/ml, 48 hr group a decrease of 18% and in the 72 hr group a decrease of 23% were observed. The intensity in the 2.0 micrograms/ml, 24 hr group decreased by 10%, and in the 2.0 micrograms/ml, 48 and 72 hr groups, it decreased more radically but a number of dead cells was recognized. From these results, the quantity of the TfR seemed to be parallel to the degree of the proliferative ability of the cancer cells. Examination with TfR can be helpful for the diagnosis and the determination of the therapeutic effect on oral cancer.

Adult↗

PubMed1990

Characterization of rat transferrin receptor cDNA: the regulation of transferrin receptor mRNA in testes and in Sertoli cells in culture.

A 3.4 kilobase cDNA complementary to rat transferrin receptor mRNA has been isolated from an adult rat testis cDNA library. The rat transferrin receptor nucleotide sequence was shown to be 82% similar to the human transferrin receptor sequence over the amino acid coding region and over 90% similar in the sequences known to be responsible for iron regulation in the human mRNA. The mRNA was shown by Northern blot analysis to be regulated by iron levels in Sertoli cells in culture. Iron depletion resulted in at least a 5-fold increase in receptor message in Sertoli cells, as well as in an actively growing testicular cell line (S10-7). The level of transferrin receptor mRNA in cultured Sertoli cells was not influenced by hormones; however, chronic administration of testosterone or FSH to hypophysectomized rats resulted in increased transferrin receptor mRNA levels in the testis. Northern blot analysis of mRNAs from testes of rats synchronized at various stages of the cycle of the seminiferous epithelium showed that transferrin receptor mRNA was differentially regulated throughout the cycle. Northern blots of mRNA from germinal cell populations derived from synchronized tests showed that the message was regulated in the nongerminal cell components of the tubule, most likely the Sertoli cell. The comparison of transferrin receptor mRNA levels in normal testes and testes from hypophysectomized rats, as well as in isolated germinal cells and cultured Sertoli cells, suggested that transferrin receptor mRNA levels were considerably higher in Sertoli cells than in other cell types of the seminiferous tubules.

Amino Acid Sequence↗

PubMed1992

Structure of the N-linked oligosaccharides of the human transferrin receptor.

Human transferrin receptor was isolated from placenta and from the hepatocarcinoma cell line Hep G2. Asparagine-linked oligosaccharides were released by treatment of tryptic glycopeptides with endo-beta-N-acetylglucosaminidase H or peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Oligosaccharide alditols were fractionated by anion-exchange high-performance liquid chromatography and by high-pH anion-exchange chromatography. Glycans from placental transferrin receptor were further characterized, after desialylation, by methylation analysis and, in part, by liquid secondary-ion mass spectrometry. Sialylation of placental transferrin receptor was examined by lectin affinity blotting with Sambucus nigra agglutinin and Maackia amurensis agglutinin. In order to trace possible inter-individual differences in N-glycosylation of the receptor, two preparations of placental transferrin receptor purified from two donors were compared. The results demonstrate that human transferrin receptor from placenta predominantly carries diantennary and triantennary N-acetyllactosaminic glycans as well as hybrid-type species, the galactose residues of which being almost completely substituted with (alpha 2-3)-linked sialic acid residues. Distinct differences were noted in the glycosylation pattern of the receptor from different individuals. Transferrin receptor from donor A carried predominantly diantennary and triantennary complex-type glycans, in part fucosylated at the innermost N-acetylglucosamine residue, in addition to small amounts of bisected and of incomplete diantennary species. Placental transferrin receptor from donor B predominantly carried triantennary N-acetyllactosaminic glycans without fucose and hybrid-type oligosaccharides with four or five mannose residues. Distinct from placental transferrin receptor, the receptor from Hep G2 cells contained larger amounts of oligomannosidic glycans with six to nine mannose residues and tetrasialylated complex-type oligosaccharides apart from mono-, di- and trisialylated species.

Agglutinins↗

PubMed1992

Identification and isolation of the Leishmania transferrin receptor.

In a previous report, we have presented several lines of evidence, derived from widely different methodologies, suggesting that Leishmania has specific receptors for transferrin with a Kd similar to the mammalian transferrin receptor. This paper describes the identification, purification, and biochemical characterization of Leishmania transferrin receptor. The Leishmania transferrin receptor, detected on intact parasites by immunoperoxidase staining, was first identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by Western blot analysis, using 125I-transferrin, as a 70-kDa protein. It has been isolated initially from Leishmania infantum promastigotes using affinity chromatography on a transferrin-Sepharose column and, subsequently, from Leishmania major promastigotes. The use of polyclonal antisera to the purified 70-kDa Leishmania transferrin receptor and to the purified rat transferrin receptor showed that the two receptors are antigenically distinct. The 70-kDa Leishmania transferrin receptor was subsequently characterized as an integral membrane glycoprotein. The monomeric state of the Leishmania transferrin receptor was demonstrated by gel filtration of purified receptor complexed with 125I-transferrin. Thus, the Leishmania transferrin receptor, unlike the mammalian receptor, is not a disulfide-linked dimer but a single 70-kDa polypeptide.

Animals↗

PubMed1991

Shedding of transferrin receptor from rat reticulocytes during maturation in vitro: soluble transferrin receptor is derived from receptor shed in vesicles.

Measurements of circulating transferrin (Tf) receptor are useful in assessing erythropoiesis; however, steps involved in the generation of soluble Tf receptor from cellular receptor are incompletely understood. To obtain a better understanding of this process, we investigated the loss of Tf receptor during terminal maturation of rat reticulocytes in vitro. Previous studies have identified Tf receptor-containing vesicles in the culture medium of maturing reticulocytes. In the present study, vesicle-free reticulocyte culture medium was found to contain functional and immunoreactive soluble Tf receptor, which increased over time. During a 44-hour incubation, Tf receptor on reticulocytes decreased by approximately 69%, while, of the Tf receptor shed to the medium, 65% was present in vesicles and 35% was in a soluble form. Isolated vesicles reincubated in fresh medium released soluble Tf receptor to the medium. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), the isolated soluble receptor protein was mainly 190 Kd and 95 Kd under nonreducing and reducing conditions, respectively, similar in size to the vesicular and cellular receptor. Our studies show that loss of Tf receptor from rat reticulocytes during maturation in vitro involves shedding of cellular Tf receptor in vesicles and release of soluble receptor from these vesicles.

Animals↗

PubMed1992

A supercoil-dependent structural alteration within the regulatory region of the human transferrin receptor gene.

The transferrin receptor gene is transcribed at low levels in quiescent cells and at much higher levels in growing or transformed cells. This regulation involves elements located within the first 114 base pairs upstream of the major transcriptional start site. This region is specifically recognized by several transacting factors and contains an element that is composed of alternating purines and pyrimidines. In vitro this element can adopt a non-B DNA conformation in a supercoil-dependent manner. Similar elements, with nearly identical spacing relative to a protein recognition sequence, can be observed in several other proliferation dependent gene promoters.

Base Sequence↗

PubMed1992

Identification of the O-linked glycosylation site of the human transferrin receptor.

The human transferrin receptor is a glycoprotein containing three N-linked and one O-linked glycosylation sites. Tryptic digestion of the receptor, followed by chromatography on BioGel P-2 and reverse-phase HPLC, yields a glycopeptide (amino acids 101-120) containing the O-linked site. Amino acid sequence analysis reveals that the site of O-glycosylation is Thr-104. Mass spectral analysis is consistent with the presence of a Gal-GalNAc core with predominantly two sialic acid residues.

Amino Acid Sequence↗

PubMed1992

Simultaneous redistribution of mannose 6-phosphate and transferrin receptors by insulin-like growth factors and phorbol ester.

Insulin-like growth factors I and II (IGF-I and IGF-II) and phorbol ester are known to induce in fibroblasts a rapid redistribution of mannose 6-phosphate (M6P)/IGF II-receptors to the cell surface. We compared the redistribution of the M6P/IGF-II receptor with that of the 46 kDa M6P receptor (MPR46) and of receptors for transferrin, low-density lipoprotein (LDL) and epidermal growth factor (EGF) in human fibroblasts under the influence of these effectors. None of the effectors altered the surface expression of receptors for LDL or EGF, which are predominantly located at the cell surface. IGF-I, IGF-II and phorbol ester increased the surface expression of the M6P/IGF-II receptor and of MPR46. The concentration of the transferrin receptor at the cell surface was increased only by IGF-I and IGF-II, with similar kinetics as for the M6P/IGF-II receptor, suggesting that the same mechanism causes redistribution. The increased surface expression of M6P receptors was accompanied by an increased uptake of receptor ligands. The number of transferrin receptors did not correlate with iron uptake, although neither the rate nor the extent of transferrin internalization was changed. These results indicate that the redistribution of several endocytic receptors induced by IGF-I, IGF-II and phorbol ester shows selectivity, and that the uptake of receptor ligand may become uncoupled from the surface expression of the receptors via distinct mechanisms.

Cells, Cultured↗

PubMed1991

Transferrin receptor expression in oral tumors.

Transferrin receptor expression in oral tumors was examined by staining with monoclonal antibody against the human transferrin receptor. The cells with positive reaction were recognized in the basal and parabasal layers of the normal epithelium. The staining was found in all the malignant tumors but not in the benign tumors. These results suggest that the immunohistochemical analysis of the transferrin receptor is useful for the diagnosis of oral malignant tumor in addition to the clinical and pathological examinations.

Antibodies, Monoclonal↗

PubMed1992

Transferrin receptor expression in myelin deficient (md) rats.

The question of iron regulation in the brain is the subject of increasing interest as the evidence continues to accumulate that a loss of brain iron homeostasis plays a significant role in some neurodegenerative diseases. Most cells acquire iron through a specific receptor mediated process involving transferrin, the iron mobilization protein. It appears that in the brain, endothelial cells, neurons, and oligodendrocytes express the transferrin receptor. This study uses a strain of rats (myelin deficient, md) in which oligodendrocytes fail to mature, and examines the consequences of this genetic defect on the expression of the transferrin receptor in the brain. The affinity of transferrin for its receptor is similar between the cerebral cortex and cerebellum in both the normal and myelin deficient rats (Kd = 7.8-10.6 nM). The transferrin receptor density is normally 2-3 times higher in the cerebellum than in the cerebral cortex. In the myelin deficient rat strain, the density of the transferrin receptor is decreased in both the cerebrum (56%) and cerebellum (70%) compared to the littermate control animals. Because oligodendrocytes are the only cell type affected in this mutant, the results suggest that these cells are responsible for a considerable amount of the transferrin receptors that are expressed in the brain (excluding the endothelial cell contributions). These observations are consistent with the existing literature stating that oligodendrocytes are responsible for the majority of transferrin and transferrin mRNA which is expressed in the brain, and support the working hypothesis that imbalances in brain iron homeostasis, particularly during development, are associated with myelin disorders.

Animals↗

PubMed1992

The human placental transferrin receptor: reconstitution into liposomes and electron microscopy.

Human transferrin receptor was isolated from Triton X-100 solubilized placental plasma membranes by a rapid one-step chromatographic procedure based on immunoadsorption of the receptor-transferrin complex on anti-transferrin Sepharose and lectin-affinity on wheat germ agglutinin. Following exchange of Triton X-100 with CHAPS or n-octylglucoside, the purified receptor was incorporated into egg phosphatidylcholine liposomes upon detergent removal by dialysis (lipid/protein ratio 15:1 to 45:1 (w/w)). Reconstitution of the receptor was confirmed by trypsin cleavage to dissociate the large extracellular receptor domain from the liposomal membranes. Electron micrographs of the receptor-lipid recombinants negatively stained with sodium sillicotungstate, showed that the receptor molecules distributed very inhomogeneously on the liposomes, most receptors being clustered. Single copies of the receptor were seen as elongate structures (5 x 10 nm) oriented with their long axis parallel to the liposome surface and separated from this by a 2-3 nm gap. This result provides evidence for a narrow connecting link between the globular extracellular receptor domain and the membrane spanning segment.

Cell Membrane↗

PubMed1991

Characterization of transferrin receptor released by K562 erythroleukemia cells.

A soluble form of transferrin receptor has been detected in human serum and has been shown recently to be a truncated form of the intact membrane bound receptor. Mechanisms governing the release of transferrin receptor by cells are poorly understood and could be better defined by tissue culture. The present investigation was undertaken to characterize the transferrin receptor released by K562 erythroleukemic cells. In contrast with maturing sheep reticulocytes, which have been shown to release transferrin receptor in small vesicles termed exosomes, we demonstrated, with a monoclonal enzyme-linked immunoassay, that less than 30% of the transferrin receptor released by K562 cells in log phase growth was in a particulate form. The relative amounts of soluble and particulate receptor released to the supernatant did not change significantly during 48 hr of incubation. Soluble receptor was purified by immunoaffinity chromatography. On polyacrylamide gel electrophoresis, its mobility was the same (85 kDa) as that of the truncated monomeric form recently identified in human serum. Further evidence that serum and soluble receptors released by K562 cells are identical was provided by amino acid sequence analysis, which demonstrated that 16 of the first 19 residues of the N-terminal sequence of soluble K562 receptor are homologous with the serum receptor. The remaining three were not identifiable. K562 cells provide a useful in vitro model for studying the production of membrane-bound and soluble forms of released transferrin receptor.

Amino Acid Sequence↗

PubMed1992

Identification and quantification of transferrin receptors on trabecular cells.

The authors identified and quantified the receptor for transferrin on trabecular meshwork (TM) cells cultured from porcine eyes by using two receptor assays. Flow-cytometric analysis of TM cells that were incubated with a monoclonal antibody to the transferrin receptor revealed such receptors, which decreased in number as the cells passed from the pre- to the post-confluent phase. Quantitative characterization by radioligand binding of 125I-transferrin to trabecular cells followed by Scatchard analysis showed that pre-confluent cultures expressed 23,839 +/- 6746 high-affinity receptors/cell and post-confluent cultures expressed 5104 +/- 3639 receptors/cell. The expression of the receptor for transferrin reflects the index of mitotic activity and can be correlated with the proliferative state of the trabecular cells. Further characterization of the receptors for transferrin in the TM may open up the possibility of a pharmacologic approach that enhances the TM cell population, which is known to decrease with age and in glaucomatous states of the eye.

Animals↗

PubMed1992

Entry of iron into cells: a new role for the transferrin receptor in modulating iron release from transferrin.

The versatile chemistry of iron and the noxious reactions this essential metal may promote have compelled iron-dependent organisms to form specific iron-binding proteins to maintain iron in soluble, nontoxic, and accessible form for cellular needs. A variety of pathways can be traversed by iron to gain access to cells, some available to all cells, others restricted to specialized cells. Of these pathways, the most important and widely functioning is uptake of iron from transferrin in a receptor-mediated process. By regulating expression of the transferrin receptor, iron-dependent cells, including neurons, can be assured an adequate supply of the essential metal while guarding against toxic excess. However, the transferrin receptor functions not only in capturing iron-bearing transferrin, but also in restraining release of iron from transferrin at the cell surface, where iron-catalyzed lipid peroxidation is a threat, while facilitating iron release in acidified endosomes to ensure safe and efficient delivery to the cell.

Animals↗

PubMed1991

Intestinal transferrin receptors and iron absorption in the neonatal rat.

The transferrin receptor is a major protein found on the basolateral membranes of intestinal epithelial cells, yet its possible role in intestinal iron metabolism and also in iron absorption is unclear. We have studied intestinal transferrin receptor expression during the peri- and postnatal development of the small intestine of the rat using immunohistochemistry with a monoclonal antibody to the rat receptor. Two major changes in transferrin receptor expression in the developing small intestine were found, a decrease in receptor expression associated with birth, and an increase at the time of weaning. Around the time of weaning there was a large decrease in iron absorption, but there was no direct correlation between absorption and transferrin receptor expression. However, at both birth and weaning there were major changes in intestinal cell kinetics, and the distribution of receptor correlated well with the distribution of proliferating cell populations. In addition, as the intestinal epithelial cells differentiated and stopped dividing, there was a redistribution of transferrin receptors from the cell surface to intracellular sites. These data suggest that the most likely role of the transferrin receptor in the neonatal intestine is in the supply of iron to the developing epithelial cells in the crypts, and that the receptor does not play a direct role in iron transit across the intestinal epithelium.

Aging↗

PubMed1991

Expression of transferrin receptors on monocytes in hemochromatosis.

To assess whether an abnormality in transferrin receptor expression or regulation could represent an underlying metabolic defect in the reticuloendothelial (RE) system in hemochromatosis, monocytes were analyzed for the expression of the transferrin receptor using a monoclonal antibody (Act II) to the transferrin receptor (CD71) and flow cytometric analysis. Hemochromatosis patients (n = 14), and normal volunteers with no clinical evidence of iron overload (n = 14) were studied. A significant inverse relationship was observed for the relationship between the expression of transferrin receptor on monocytes and log(hepatic iron concentration) in hemochromatosis patients (r = -0.59, P less than .02) and also for the relationship between the expression of transferrin receptor and log(serum ferritin) in normal volunteers (r = -0.90, P less than .001). There was no significant difference in the mean expression of monocyte transferrin receptor between hemochromatosis patients and normal volunteers. However, the expression of the transferrin receptor in hemochromatosis patients was disproportionately higher than would be predicted from the relationship between serum ferritin and transferrin receptor expression in normal volunteers. The inverse relationship of the monocyte transferrin receptor relative to body iron stores in hemochromatosis is consistent with observations in other tissues, and suggests that non-transferrin iron metabolism, including ferritin, requires further investigation in the RE cell in hemochromatosis.

Antibodies↗

PubMed1991

Distribution and number of transferrin receptors in Parkinson's disease and in MPTP-treated mice.

Transferrin is a glycoprotein that functions primarily to deliver iron to the cell. Recent studies suggest that the transferrin receptor mediates the intracellular delivery and transport of iron bound to transferrin in the CNS. Iron-catalyzed free radical generation has been proposed as a possible cause of nigral cell death in Parkinson's disease. Our hypothesis is that abnormal iron handling by the transferrin receptor may contribute to the formation of free radical species which catalyze the lipid peroxidation of nigral cell membranes. We have assessed the number of transferrin receptors on membrane fractions prepared from the human striatum from control subjects and patients with Parkinson's disease. Equilibrium-binding studies demonstrated a reversible, saturable, and high-affinity transferrin binding site (KD = 3 nM) in human brain membranes. Regional binding assays indicate that the number of transferrin receptors in the putamen was reduced significantly in Parkinson's disease. The density of transferrin receptors was unaltered in membranes prepared from the caudate nuclei and the globus pallidus. To address the possibility that transferrin receptors are located on dopaminergic terminals, we have examined the distribution and number of transferrin receptors in the striatum of MPTP-treated mice using in vitro autoradiographic methods. In these experiments, the loss of dopaminergic terminals in the striatum was visualized by differential [3H]mazindol uptake site autoradiography. A marked reduction in the density of both transferrin receptors and [3H]mazindol binding sites was observed in the mouse striatum 7 days post-MPTP treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗