Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Transferrin”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 973 records · Page 54Linked to original sources
PubMed1993

Increased biliary transferrin excretion following parenteral aluminium administration to rats.

Aluminium accumulates in the livers of patients receiving either parenteral nutrition or haemodialysis. When given parenterally to rats, aluminium causes cholestasis. However, the mechanism of hepatic aluminium uptake and the fate of aluminum in the liver are poorly understood. We examined the effect of parenteral aluminium administration on biliary excretion of transferrin, the major circulating aluminum-binding protein. Male Wistar rats were given parenterally aluminum 5 mg/kg/day for 1-14 days. Bile was collected for 3 hr at the end of the study period. Biliary total protein concentration and IgA/total protein were unaffected by up to 14 days of parenteral aluminium administration. However, biliary transferrin excretion increased with duration of aluminum administration up to five-fold by day 14. Biliary transferrin concentration and transferrin/total protein was higher in aluminum treated rats than controls after 7 and 14 days of study. Hepatic aluminum concentration reached a maximum after 4 days of parenteral aluminum administration, at which time serum bile acid and alanine amino transferase values were not different from controls. Since biliary transferrin is normally derived from the serum, it is likely that aluminum promotes hepatocellular uptake of transferrin and that aluminum enters the hepatocyte bound to transferrin. We postulate that transferrin may direct aluminum to intracellular sites where its toxic effects would be minimized.

Alanine Transaminase↗
PubMed1998

Levels of antibodies to transferrin and alpha 2-HS glycoprotein in women with and without endometriosis.

PROBLEM: To establish an enzyme-linked immunosorbent assay (ELISA) for determining the levels of antibodies to transferrin and alpha 2-HS glycoprotein in the serum of women with and without endometriosis. METHOD OF STUDY: Serum samples were obtained from 105 normal women, who were randomly selected for a population-based epidemiologic study, and 123 patients with active endometriosis. An ELISA using transferrin and alpha 2-HS glycoprotein as antigens was established. RESULTS: The levels of antibodies to transferrin and alpha 2-HS glycoprotein in the serum of patients with endometriosis were approximately 21 times higher than those in the serum of control subjects without endometriosis. Only 2% of control subjects had false positive levels of these antibodies, and 5% of patients with endometriosis had false negative levels of these antibodies (specificity, 98.1 and 98.1, respectively, for anti-transferrin and anti-alpha 2-HS glycoprotein; sensitivity, 95 and 96.7, respectively, for anti-transferrin and anti-alpha 2-HS glycoprotein). CONCLUSIONS: Patients with endometriosis have significantly higher levels of antibodies to transferrin and alpha 2-HS glycoprotein than control subjects. Testing women for antibodies to transferrin and alpha 2-HS glycoprotein will provide a specific noninvasive diagnosis of endometriosis.

Adolescent↗
PubMed1980

The role of plasma transferrin in iron absorption in the rat.

The question of whether plasma transferrin acts as a carrier of iron from intestinal mucosal cells to the blood plasma was investigated in a series of experiments in the tat. By thoracic duct cannulation and collection of lymph during absorption it was confirmed that nearly all absorbed iron passes directly to portal blood. The total rate of transcapillary exchange of transferrin and the rate of passage of plasma transferrin into the extravascular compartment of the intestinal mucosa were then measured in separate groups of rats. The rate of exchange were insufficient for transferrin to act as the carrier of iron at the rate at which it passes from intestinal cells to portal plasma after ingesting a dose of inorganic iron. Some specific binding of transferrin and cellular uptake of iron by intestinal mucosa was observed after the intravenous injection of transferrin labelled with 59Fe and 125I. It is concluded from these experiments that absorbed iron passes from intestinal cells to portal plasma largely in a low molecular weight form. The passage of plasma transferrin into the interstitial fluid of the intestinal mucosa and binding to mucosal cells probably functions primarily to supply iron to the cells and not to act as a carrier of iron from the cells.

Animals↗
PubMed1996

Protease cleavage of iron-transferrin augments pyocyanin-mediated endothelial cell injury via promotion of hydroxyl radical formation.

Although a number of bacterium- and host-derived factors have been suggested to contribute to the pathogenesis of Pseudomonas aeruginosa-associated tissue injury, the mechanism remains unclear. We have previously shown that protease modification of iron (Fe)-transferrin generates new iron chelates capable of catalyzing hydroxyl radical (.OH) formation from superoxide and hydrogen peroxide. The latter two oxidants are generated during redox cycling of another P. aeruginosa secretory product, pyocyanin. The lung is a major site of P. aeruginosa infection, with damage to local endothelial cells contributing to the pathogenesis of such infections. Endothelial cells are highly susceptible to oxidant-mediated injury. Therefore, we examined whether pseudomonas elastase-cleaved Fe-transferrin and pyocyanin synergistically enhance pulmonary artery endothelial cell injury via .OH formation. By measuring 51Cr release from cultured endothelial cell monolayers, pseudomonas elastase-cleaved Fe-transferrin significantly augmented cell injury resulting from cellular exposure to sublethal concentrations of pyocyanin. This enhancement in injury was not protease specific, as similar results were obtained with pyocyanin in combination with trypsin- or porcine pancreatic elastase-cleaved Fe-transferrin. The association of iron with the transferrin appeared to be necessary in this process. Supporting the involvement of .OH generation via the Haber-Weiss reaction in augmenting cell injury, catalase, dimethyl thiourea, superoxide dismutase, deferoxamine, and dimethyl sulfoxide significantly inhibited cell injury resulting from exposure to pyocyanin and protease-cleaved Fe-transferrin. Furthermore, spin trapping demonstrated the production of .OH in this cellular system. We conclude that .OH formation resulting from the interaction of protease-cleaved Fe-transferrin and endothelial cell redox cycling of pyocyanin may contribute to P. aeruginosa-associated tissue injury via endothelial cell injury.

Animals↗
PubMed2001

Characterization of a novel transferrin receptor in bovine strains of Pasteurella multocida.

Analysis of bovine respiratory isolates of Pasteurella multocida demonstrated that six of nine strains tested were capable of growth dependent upon bovine transferrin and of specifically binding ruminant transferrins. A single 82-kDa protein was affinity isolated from the P. multocida strains with immobilized bovine transferrin. In contrast to what has been observed in other species, binding of this protein to immobilized transferrin was specifically blocked by the N-lobe subfragment of bovine transferrin. A single gene encoding the 82-kDa protein was flanked by a leucyl-tRNA synthetase gene and an IS1060 element, in contrast to other species where genes encoding the two receptor proteins (TbpB and TbpA) are found in an operonic arrangement. A similar gene arrangement was observed in all of the receptor-positive strains, in spite of the observation that they belonged to different genomic groups. Analysis of the deduced amino acid sequence of the receptor protein indicated that it is a member of the TonB-dependent outer membrane receptor family, and although it is related to transferrin and lactoferrin receptor proteins (TbpAs and LbpAs) from other species, it differs substantially from other members of this group. Amino acid alignments suggest that the reduced size (20 kDa smaller) of the P. multocida TbpA is primarily due to the absence of larger predicted external loops. Collectively these results suggest that P. multocida has a single, novel receptor protein (TbpA) that is capable of efficiently mediating iron acquisition from bovine transferrin without the involvement of a second receptor protein (TbpB).

Amino Acid Sequence↗
PubMed2002

Demonstration and characterization of a specific interaction between gonococcal transferrin binding protein A and TonB.

Iron scavenging by Neisseria gonorrhoeae is accomplished by the expression of receptors that are specific for host iron-binding proteins, such as transferrin and lactoferrin. Efficient transferrin-iron acquisition is dependent on the combined action of two proteins, designated TbpA and TbpB. TbpA is a TonB-dependent outer membrane receptor, whereas TbpB is lipid modified and serves to increase the efficiency of transferrin-iron uptake. Both proteins, together or separately, can be isolated from the gonococcal outer membrane by using affinity chromatography techniques. In the present study, we identified an additional protein in transferrin-affinity preparations, which had an apparent molecular mass of 45 kDa. The ability to copurify this protein by transferrin affinity was dependent upon the presence of TbpA and not TbpB. The amino-terminal sequence of the 45-kDa protein was identical to the amino terminus of gonococcal TonB, indicating that TbpA stably interacted with TonB, without the addition of chemical cross-linkers. Using immunoprecipitation, we could recover TbpA-TonB complexes without the addition of transferrin, suggesting that ligand binding was not a necessary prerequisite for TonB interaction. In contrast, a characterized TonB box mutant of TbpA did not facilitate interaction between these two proteins such that complexes could be isolated. We generated an in-frame deletion of gonococcal TonB, which removed 35 amino acids, including a Neisseria-specific, glycine-rich domain. This mutant protein, like the parental TonB, energized TbpA to enable growth on transferrin. Consistent with the functionality of this deletion derivative, TbpA-TonB complexes could be recovered from this strain. The results of the present study thus begin to define the requirements for a functional interaction between gonococcal TbpA and TonB.

Amino Acid Sequence↗
PubMed1991

Transferrin glycosylation in hypoxia.

The aim of this study was to examine the effect of reduced O2 tension on the glycosylation of transferrin. Rats were placed in a hypobaric chamber (380 mmHg) that corresponded to an altitude of 5486 m above sea level for 21 days. The animals responded with marked increases in hematocrit (from 44 to 76%) and cardiac weight, and with reductions in the concentration of plasma transferrin averaging 15%. Analyses of their plasma transferrin by serial anion-exchange and lectin affinity chromatography revealed no changes in the extent of glycan branching. However, there was a moderate rise in the proportion of fucosylated transferrin molecules (fucosylation index) and a slight decrease in the transferrin fraction bearing a tetrasialylated biantennary glycan. The fucosylation index correlated positively with plasma transferrin concentrations in the test animals, but not in the controls. In contradistinction to the situation with transferrin, hypoxic rats exhibited a reduced fucosylation index of immunoglobulin G.

Animals↗
PubMed1988

Growth factor effects on small cell lung cancer cells using a colorimetric assay: can a transferrin-like factor mediate autocrine growth?

A semiautomated colorimetric assay (MTT assay), based on the ability of live cells to reduce a tetrazolium-based compound, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), to a purplish colored formazan product that can be measured spectrophotometrically, has recently been adapted for use in drug sensitivity analysis of cultured human tumor cell lines. We report the application of this assay for the evaluation of the growth factor requirements of human small cell lung cancer (SCLC) cell lines. Specifically, the growth stimulation of each constituent of a previously reported serum-free defined medium system for SCLC including various concentrations of hydrocortisone, insulin, transferrin, 17 beta-estradiol, and selenium (HITES) was evaluated. The optimal concentrations for insulin, transferrin, and selenium derived in the previously reported experiments with direct counting of viable cells were similar to optimal concentrations determined for the growth of three SCLC cell lines (NCI-H82, NCI-N417, NCI-H526) using the MTT assay. In contrast to the previous report, the growth-stimulating effects of hydrocortisone and 17 beta-estradiol were negligible. Using the MTT we have shown that a SCLC cell line, NCI-H345 (which has been previously reported to produce a transferrin-like molecule), was growth-inhibited by an anti-transferrin receptor antibody, when grown in transferrin-free media. The conditioned media from this cell line is stimulatory to other transferrin-sensitive cell lines, suggesting the possibility of an autocrine role for this transferrin-like molecule at least in that cell line. With carefully defined conditions for a given cell line in which cell density and other parameters are within a range of constant MTT metabolism, the assay is well suited for precise analysis of growth factor effects.

Carcinoma, Small Cell↗
PubMed1982

Effect of iron saturation on transferrin uptake by reticulocytes. A morphological study.

The presence of iron on the transferrin molecule increases its affinity for and sojourn time on the reticulocyte. This could be due to selective internalization of iron-containing transferrin molecules. This possibility was investigated by electron microscopic autoradiography. Rabbit reticulocytes were incubated with rabbit transferrin at 6, 33, and 72% iron saturations, and the distribution of transferrin molecules at membrane and intracellular locations was assessed by grain counting. The results showed that (1) both apotransferrin and iron transferrin enter the cell interior and (2) the amount of intracellular transferrin was primarily controlled by the concentration of membrane-bound transferrin and not by its iron saturation.

Animals↗
PubMed1979

[Anemia in malignant tumors. Loss of circulating transferrin due to lysosomal storage in human and rat malignant tumors].

The cellular uptake of 67Ga-labelled transferrin was studied in the carcinoma of the human respiratory tract and in the Morris hepatoma 5123 C of the rat. In both types of tumors a positive tumor imaging by 67Ga-transferrin scintigraphy was evident. The intracellular distribution pattern of the radioactivity showed that the incorporated 67Ga-transferrin is accumulated within the lysosomes of the tumors. The uptake of 67Ga-transferrin by the tumor cells resulted in a faster disappearance of the tracer from the blood. The accelerated disappearance of 67Ga-transferrin from the blood showed a direct correlation to the mass of tumor cells. The loss of circulating 67Ga-transferrin from the blood showed a close parallelism to the grade of the anemia observed in the tumor bearing rats. We conclude from these findings that the uptake of transferrin into the tumor cells is one of the factors which are responsible for the anemia observed in malignant diseases.

Aged↗
PubMed1982

Studies of the transferrin receptor on both human reticulocytes and nucleated human cells in culture: comparison of factors regulating receptor density.

The transferrin receptor, present on reticulocytes and nucleated cells in tissue culture, has been measured with both immunoassay techniques and transferrin binding studies. The total cellular immunoreactive receptor is rapidly lost from erythrocytes during the process of reticulocyte maturation (from as many as 400,000 molecules to <20,000 molecules/reticulocyte). This event parallels the loss of cell surface transferrin binding sites and RNA content, and correlates with previous studies that have measured the decline in hemoglobin synthesis.Nonhemoglobin-producing normal human fibroblasts, which appear to have a much lower iron requirement than reticulocytes, contain similar numbers of immunoreactive receptors per cell (400,000 receptor molecules), when in an active state of proliferation. Although receptor density on fibroblasts is directly related to cell proliferation, our studies demonstrate that nonproliferating fibroblasts still retain significant numbers of immunoreactive receptors (150,000 molecules/cell) and transferrin binding sites. Since additional studies indicate that proliferating cells have increased iron uptake, a simple hypothesis would predict that the parallel increase in transferrin binding sites and total cellular immunoreactive receptor associated with proliferation is related to an increased cellular iron requirement. However, the number of immunoreactive receptor molecules and transferrin binding sites is not changed when cells are grown in iron-deficient media, or in media with added transferrin-iron. This result and the lack of marked differences in receptor number on both hemoglobin-producing and nonhemoglobin-producing cells indicate that other factors besides receptor density play major roles in the regulation of cellular iron uptake, retention, and loss.

Anemia, Sickle Cell↗
PubMedDate not supplied

Transferrin--a poor measure of nutritional status.

The present study evaluated the sensitivity and specificity of the serum transferrin concentration as a measure of the nutritional state. Serum transferrin was derived from total iron-binding capacity measurements in 74 patients on 114 occasions and correlated with body composition as measured by multiple isotope dilution. Highly significant correlations (p less than 0.001) existed between serum transferrin and both the body cell mass and the nutritional state as measured by the Nae/Ke ratio. However, the 95% confidence limits about both regressions were wide. The false-positive rate was 60% while the false-negative rate was 31%. Body composition and transferrin were measured before and after 2 wk of total parenteral nutrition in 34 malnourished patients. Eighteen patients restored body cell mass toward normal after 2 wk of total parenteral nutrition while in 16 patients the body cell mass continued to decrease in size, despite 2 wk of total parenteral nutrition. The changes in serum transferrin were not significant over this period of time in either group, despite significant changes in the nutritional state in both groups. The presence of a statistically significant relationship between the serum transferrin concentration and the nutritional state indicates that the serum transferrin concentration accurately reflects a population's nutritional status, and is therefore useful in epidemiologic surveys. However, because of the large variance of the data, as demonstrated by the wide 95% confidence limits, and because of the poor sensitivity and specificity, in an individual patient it is of little value as a measure of the nutritional status.

Body Composition↗
PubMed1998

Immunocytochemical development of transferrin and ferritin immunoreactivity in the human pons and cerebellum.

The distribution and development of transferrin-positive cells in the pons and cerebellum of human fetuses to adults were examined immunohistochemically, compared with those of ferritin-positive cells. Transferrin was present in oligodendrocytes, astrocytes, and neurons. Transferrin-positive neurons appeared at 18 weeks of gestation in Purkinje cells and the pontine reticular formation. In the pontine nuclei, transferrin-positive neurons appeared at 22 weeks of gestation. On the other hand, transferrin-positive glia also appeared at 18 weeks of gestation in the reticular formation, and at 24 weeks of gestation in the cerebellar white matter and pontine nuclei. Transferrin-positive glia and cells appeared earlier in the reticular formation of the pons than ferritin, but the order of its appearance was similar to that of ferritin and myelination. Because iron is involved in the syntheses and functions of dopamine, serotonin, and gamma-aminobutyric acid (GABA), transferrin may be carried for various iron uses from an early fetal stage.

Adult↗
PubMed2006

Monoclonal immunoglobulin with antitransferrin activity: A rare cause of hypersideremia with increased transferrin saturation.

Two unusual but similar cases of very high serum iron, extremely high transferrin concentrations (5.4 to 6.5 g/L), and increased transferrin saturation are reported. No anemia or microcytosis was observed. The ferritin concentration remained within the normal range, and no iron overload was observed. In one case, the in vivo half-life of 59Fe-labeled transferrin was shown to be prolonged (206 minutes versus 75 minutes for controls). In both patients, a monoclonal IgG was observed in the serum. The association between serum transferrin and monoclonal IgG was demonstrated by Western blot analysis and affinity chromatography. We suggest that the transferrin bound to the monoclonal IgG molecule has a prolonged half-life in the circulation, leading to high transferrin concentrations, and that the increased serum iron values prevent the onset of anemia. The antitransferrin activity of monoclonal antibody should be added to the list of situations accounting for elevated serum iron with elevated transferrin saturation.

Antibodies, Monoclonal↗
PubMed1984

Regulation of transferrin secretion by human Sertoli cells cultured in the presence or absence of human peritubular cells.

Transferrin represents 1-4% of the total proteins secreted by human Sertoli cells, and the amount secreted by the cells was maximal after a 4- to 5-day period in culture, the time chosen for each medium change. During this first 4- to 5-day period, the addition of FSH, insulin, (Bu)2cAMP, and isobutylmethylxanthine had no effect on transferrin secretion; however, from days 4-5 to 8-10, each of the above compounds significantly stimulated transferrin secretion compared to control values. Testosterone (in the absence or presence of insulin) had no effect. Transferrin secretion increased for the first 5 days in culture, with a similar magnitude in the presence or absence of the above stimulators, and thereafter declined, more so in untreated cultures. These results suggest that these agents do not stimulate, but, rather, limit the decline in transferrin secretion. When human peritubular cells were cocultured with Sertoli cells, transferrin secretion was significantly elevated compared to that by Sertoli cells alone. Interestingly, in the cocultures (Bu)2cAMP stimulated transferrin secretion when added for the first 4- to 5-day culture period. Human fibroblasts or spent medium from the peritubular cell cultures did not mimic the effect found when peritubular and Sertoli cells were cocultured. These results provide evidence that peritubular cells play a critical role in regulating human Sertoli cell function.

1-Methyl-3-isobutylxanthine↗
PubMed1996

GLUT4 in cultured skeletal myotubes is segregated from the transferrin receptor and stored in vesicles associated with TGN.

There is little consensus on the nature of the storage compartment of the glucose transporter GLUT4, in non-stimulated cells of muscle and fat. More specifically, it is not known whether GLUT4 is localized to unique, specialized intracellular storage vesicles, or to vesicles that are part of the constitutive endosomal-lysosomal pathway. To address this question, we have investigated the localization of the endogenous GLUT4 in non-stimulated skeletal myotubes from the cell line C2, by immunofluorescence and immunoelectron microscopy. We have used a panel of antibodies to markers of the Golgi complex (alpha mannosidase II and giantin), of the trans-Golgi network (TGN38), of lysosomes (lgp110), and of early and late endosomes (transferrin receptor and mannose-6-phosphate receptor, respectively), to define the position of their subcellular compartments. By immunofluorescence, GLUT4 appears concentrated in the core of the myotubes. It is primarily found around the nuclei, in a pattern suggesting an association with the Golgi complex, which is further supported by colocalization with giantin and by immunogold electron microscopy. GLUT4 appears to be in the trans-most cisternae of the Golgi complex and in vesicles just beyond, i.e. in the structures that constitute the trans-Golgi network (TGN). In myotubes treated with brefeldin A, the immunofluorescence pattern of GLUT4 is modified, but it differs from both Golgi complex markers and TGN38. Instead, it resembles the pattern of the transferrin receptor, which forms long tubules. In untreated cells, double staining for GLUT4 and transferrin receptor by immunofluorescence shows similar but distinct patterns. Immunoelectron microscopy localizes transferrin receptor, detected by immunoperoxidase, to large vesicles, presumably endosomes, very close to the GLUT4-containing tubulo-vesicular elements. In brefeldin A-treated cells, a network of tubules of approximately 70 nm diameter, studded with varicosities, stains for both GLUT4 and transferrin receptor, suggesting that brefeldin A has caused fusion of the transferrin receptor and GLUT4-containing compartments. The results suggest that GLUT4 storage vesicles constitute a specialized compartment that is either a subset of the TGN, or is very closely linked to it. The link between GLUT4 vesicles and transferrin receptor containing endosomes, as revealed by brefeldin A, may be important for GLUT4 translocation in response to muscle stimulation.

Animals↗
PubMed2003

Mass spectrometric analysis of human transferrin in different body fluids.

In this study, we present a versatile new procedure for the analysis of transferrin and its isoforms isolated from human body fluids such as serum, plasma, and cerebrospinal fluid. This method is based on a three-step procedure: (i) isolation of transferrins using anion-exchange chromatography with UV detection; (ii) concentration of the transferrin fraction; (iii) detection of the transferrins with liquid chromatography-electrospray mass spectrometry. Pre-analytical sample procedures can be omitted and no immunoaffinity columns or transferrin-specific immunoassays were used. Anticoagulants such as heparin, EDTA, citrate, and oxalate do not interfere with our analysis. According to their respective molecular masses, up to ten different isoforms of transferrin could be identified in a serum sample from a patient with a congenital disorder of glycosylation type Ia (CDG-Ia). The method was successfully applied to different pathological samples from patients with CDG-Ia, CDG-Ib, CDG-Ic, CDG-Ie, CDG-If, and CDG-IIa. Additionally, samples from alcohol consumers that were found with turbidimetric immunoassay to contain increased levels of carbohydrate-deficient transferrin were analyzed.

Body Fluids↗
PubMed1994

Variation of transferrin mRNA concentration in the rabbit mammary gland during the pregnancy-lactation-weaning cycle and in cultured mammary cells. A comparison with the other major milk protein mRNAs.

The concentration of transferrin mRNA was evaluated during pregnancy and lactation in rabbit mammary gland and liver using northern blot and dot blot assays. Transferrin mRNA was present in the virgin rabbit mammary gland and its concentration increased as pregnancy proceeded, with a major enhancement after day 15. A high concentration was reached 3 days after parturition, with no additional increase during lactation and with a marked decline after weaning. During the same period, the concentration of transferrin mRNA showed only a very weak variation in liver. This mRNA was six times more abundant in mammary gland than in liver of lactating rabbit. The accumulation of transferrin mRNA in the mammary gland was concomitant with the accumulation of alpha s1-, beta-, kappa-casein and WAP (whey acidic protein) mRNAs. The concentration of glyceraldehyde 3-phosphate dehydrogenase mRNA, taken as a non-inducible control mRNA, declined progressively during pregnancy to reach its lower level in lactation. These observations suggest that casein, WAP and transferrin mRNAs are subjected to a similar control mechanism in vivo, at least in the second half of pregnancy and during lactation. Experiments carried out in vitro using isolated rabbit epithelial mammary cells cultured on collagen I gel indicated that transferrin mRNA was abundant and only weakly inducible by the lactogenic hormones insulin, cortisol and prolactin, as opposed to caseins and WAP mRNAs. R5020, an analogue of progesterone, inhibited at most very slightly the accumulation of alpha s1-casein mRNA in the presence of prolactin and it did not reduce the expression of transferrin gene.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗