Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A soluble tryptic fragment of the human transferrin receptor (residues 121 to 760) has been crystallized from 2.8 M-KCl (pH 6.2) and polyethylene glycol 8000. This fragment retains the transferrin-binding activity of intact transferrin receptor. Although the trypsin treatment removes the intermolecular disulfide bonds, the receptor fragment is dimeric both under physiological conditions and at the high salt concentrations used for crystallization. The receptor fragment crystallizes in the orthorhombic space group P2(1)2(1)2(1), a = 105.5 A, b = 224.5 A, c = 363.5 A. The crystals are extremely radiation sensitive. Their diffraction extends to 3.8 A, and there is some diffuse scatter with helical characteristics. Analysis of these diffraction patterns indicates that the transferrin receptor fragments are arranged in continuous 8-fold symmetric helical columns parallel to the c axis, with a total of 32 receptor fragment monomers in the unit cell. A structure determination is in progress.
J Mol Biol 1991 Apr 20
PMID:Crystallization and X-ray diffraction studies of a soluble form of the human transferrin receptor. 202 43

Placental transferrin receptors, located at the apical side of syncytiotrophoblast, mediate placental iron uptake. Regulation of transferrin receptors on the fetal-maternal exchange area could be a major determinant in the regulation of trans-placental iron transport. Transferrin receptor expression in cultured human term cytotrophoblasts is on a much lower level than in choriocarcinoma cells, with a higher proportion of receptors located on the cell surface. Differentiation of cells, either due to longer culture periods or to 8-bromo-cAMP treatment does not lead to an increase of transferrin receptor expression. In vitro, the level of expression is largely regulated by the cellular density in the culture dishes. Low cellular occupancy of the dish leads to a high level of transferrin receptors. Treatment with iron-sources results in a down regulation of transferrin receptors. Thus, though the level of transferrin receptors in cultured normal trophoblast is at a constant level, unaffected by differentiation, high levels of maternal transferrin-iron availability can lead to a decrease in placental iron uptake. This feed-back mechanism makes placental iron uptake independent of maternal iron stores.
Mol Cell Biochem 1991 Jan 16
PMID:Transferrin receptor expression and the regulation of placental iron uptake. 205 96

The acute and chronic effects of basic fibroblast growth factor (bFGF) on transferrin (TF) secretion from Sertoli cells were investigated by using reverse hemolytic plaque assays which enabled the visualization of release from individual cells in culture. We found that acute treatment with bFGF stimulates the release of TF from some but not al Sertoli cells in cultures obtained from 20-day-old rats. Chronic treatment with this growth factor resulted in increases in overall cell number in cultures from animals of each age tested (8-20 days of age). In contrast, this long-term treatment decreased markedly the proportions of Sertoli cells that secreted TF but only in cultures from 10-day-old animals. When taken together, these findings of acute and chronic influences of bFGF on TF secreting cells support the possibility that bFGF not only contributes to the modulation of the day-to-day release of certain substances from Sertoli cells, but may also influence development of the portions of the cell population that secrete these substances.
Mol Cell Endocrinol 1990 Oct 22
PMID:Fibroblast growth factor modulates the release of transferrin from cultured Sertoli cells. 212 83

Oxygen-derived free radicals have been implicated in damage to membrane phospholipids leading to alterations in membrane function. The purpose of this study was to investigate alterations in intracellular ionic calcium (Ca2+) levels and Ca2+ transients, cellular morphology, conjugated diene levels, arachidonate release, and lactate dehydrogenase release resulting from the exposure of cultured neonatal rat ventricular myocytes to a xanthine oxidase catalyzed free radical generating system capable of producing superoxide and hydroxyl radicals. The ability of alpha-tocopherol to prevent alterations due to free radical exposure was investigated. For measurements of Ca2+, myocytes grown on coverslips for 3-4 days were loaded with fura-2/AM and studied by microspectrofluorometry. Control myocytes superfused with a physiological buffer or buffer containing purine and iron-loaded transferrin exhibited Ca2+ transients associated with spontaneous contractions. For control, buffer perfused myocytes (n = 4), the fura-2 340/380 ratios were 0.5 +/- 0.1 (mean +/- S.E.) and 1.6 +/- 0.03 at the minimum and maximum, respectively, of the Ca2+ transient, after 1 h of perfusion. Exposure to the free radical generating solution (n = 14) altered intracellular Ca2+. The 340/380 minimum ratio was 639% of the control value after approximately 30-70 mins with cessation of normal Ca2+ transients. Bleb development was associated with increased Ca2+. Myocytes reperfused with control medium continued to exhibit an elevated minimum fura-2 ratio at 687% of control. Myocytes pretreated with 10 microM alpha-tocopherol (n = 13) for 18-24 h and exposed to free radicals did not exhibit increases in intracellular Ca2+, having a minimum 340/380 ratio of 0.5 +/- 0.1 after 60-90 mins, and although myocytes often ceased contracting, they resumed spontaneous Ca2+ transients with control medium reperfusion and also maintained normal structure. Exposure of myocyte cultures to free radical generating solutions resulted in increased levels of conjugated dienes and increased release of [3H]arachidonate and lactate dehydrogenase compared to control values after 1 h. alpha-Tocopherol treatment attenuated the increase in conjugated diene levels, and the release of [3H]arachidonate and lactate dehydrogenase. Thus, free radicals alter intracellular Ca2+, conjugated dienes and membrane structure indicating their ability to induce altered ionic homeostasis in association with myocardial membrane damage. alpha-Tocopherol decreased free radical mediated injury.
J Mol Cell Cardiol 1990 Sep
PMID:Free radicals alter ionic calcium levels and membrane phospholipids in cultured rat ventricular myocytes. 212 94

The influence of rat round spermatid protein(s) (RSP) on protein synthesis and secretory function of Sertoli cells was used in the bicameral chamber system. Round spermatids (RS) were purified from 90-day-old rats by centrifugal elutriation. RS were incubated in a supplement-enriched culture medium that lacked exogenous proteins. The RS-conditioned media were dialysed and lyophilized to obtain RSP. Most de novo protein synthesized under basal conditions by Sertoli cells (18-day-old) was secreted into the apical chamber (apical/basal ratio: 3.42). Follicle-stimulating hormone (FSH, 100 ng/ml) stimulated total protein secretion from Sertoli cells by a factor of 1.54. The RSP (100 micrograms/ml) stimulated total protein secretion from Sertoli cells by a factor of 2.33. The enhancement of total Sertoli cell protein secretion by FSH and RSP additively increased by a factor of 2.82. The combined effect of FSH and RSP on total protein secretion from Sertoli cells was dose dependent and saturated at approximately 200 micrograms/ml of RSP. Polarity of total protein secretion from Sertoli cells (apical/basal ratio: 3.42) was stimulated by RSP predominantly in the apical direction (apical/basal ratio: 8.48). The modulation of radiolabeled Sertoli cell secretory proteins (ceruloplasmin, CP; sulfated glycoprotein-2, SGP-2; testins and transferrin, Tf) by cold (non-labeled) RSP was investigated by immunoprecipitation followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The secretion of CP, SGP-2 and Tf was stimulated in a dose-dependent manner by the addition of RSP up to a saturating concentration of between 200 and 300 micrograms/ml, whereas the secretion of Sertoli cell testins did not reach saturation at 300 micrograms/ml RSP. These results indicate that FSH and RSP independently modulate Sertoli cell protein secretion, and that Sertoli cell secretory proteins may differentially respond to RSP stimulation.
Mol Cell Endocrinol 1990 Oct 01
PMID:Modulation of Sertoli cell secretory function by rat round spermatid protein(s). 212 59

Effects of catecholamines on DNA synthesis in vascular smooth muscle cells (VSMC) were investigated in a chemically defined medium that included insulin, transferrin, and sodium selenite. Smooth muscle-rich preparation was obtained from rat aortic media and VSMC were further purified by cell cloning. A clone that was positive for smooth muscle actin and was negative for the coagulation factor VIII was used in this study. The fetal calf serum-induced proliferation was enhanced by alpha-adrenergic and inhibited by beta-adrenergic stimulation. When cells of low passages were used, dose-response curves for norepinephrine were biphasic; when cells were subconfluent, norepinephrine stimulated DNA synthesis at as low as 1 nM and was apparently ineffective at more than 100 nM. When cells were confluent, the effect of norepinephrine was inhibitory at lower concentrations (less than 1 nM) and stimulatory at relatively higher concentrations. Cells of higher passages exhibited only inhibitory effects of the amine. Stimulatory and inhibitory effects on DNA synthesis were mediated through alpha 1- and beta 2-adrenergic receptors, respectively. Thus, the alpha 1-agonist phenylephrine was more potent than the alpha 2-agonist clonidine in stimulating DNA synthesis. An alpha 1-adrenergic antagonist, prazosin, was more effective than the alpha 2-adrenergic antagonist yohimbine in antagonizing the stimulatory effect of norepinephrine. beta-Adrenergic agonists inhibited DNA synthesis with IC50 values in the nanomolar range; the rank order of potency of agonists was isoproterenol greater than salbutamol greater than or equal to (-)-epinephrine much greater than (-)-norepinephrine, consistent with beta 2-receptor specificity. (+)-Epinephrine or (+)-norepinephrine, the stereoisomers of the catecholamines, were ineffective. The inhibitory effects of norepinephrine were reversed by beta-adrenergic antagonists, with the rank order of potency of pindolol greater than butoxamine greater than atenolol, consistent with beta 2-receptor specificity. The dose-response curves of norepinephrine, therefore, seemed to be determined by a balance between alpha 1-receptor-mediated stimulation and beta 2-receptor-mediated inhibition of DNA synthesis. Minimum time required for exhibiting alpha 1-adrenergic or beta 2-adrenergic effects was between 6 and 15 hr, suggesting that the G0 or G1 phase of the cell cycle might be the site of action. These results show that catecholamines dually modulate DNA synthesis in VSMC through specific adrenergic receptors.
Mol Pharmacol 1990 Jan
PMID:Alpha 1-adrenergic stimulation and beta 2-adrenergic inhibition of DNA synthesis in vascular smooth muscle cells. 215 7

Disaggregated airway epithelial cells replicate in serum-free media containing supraphysiologic concentrations of insulin. To examine the hypothesis that the type 1 insulin-like growth factor (IGF) receptor mediates the mitogenic action of insulin on these cells, we studied the mitogenic effects of IGF-I and insulin, and the expression of type 1 IGF receptors in primary cultures of adult canine tracheal epithelial cells. Isolated tracheal epithelial cells were grown in varying concentrations of IGF-I or insulin in Ham's F12 medium supplemented with transferrin, cholera toxin, and endothelial cell growth supplement. Both IGF-I and insulin increased DNA synthesis (measured as [3H]thymidine incorporation into DNA) and cell number in a concentration-dependent fashion, but IGF-I was at least 20 to 60 times more potent than insulin in its mitogenic effects. No additive or synergistic effect was observed with the simultaneous addition of IGF-I and insulin in maximally effective doses. A monoclonal antibody directed against the type 1 IGF receptor (alpha IR3) blocked the mitogenic activity of both IGF-I and insulin. Affinity labeling of type 1 IGF receptors by covalent cross-linking with disuccinimidyl suberate demonstrated the tracheal epithelial cell IGF-I binding moiety to have a relative molecular weight of 130,000 D. Binding of [125I]IGF-I to this protein was inhibited by low concentrations of IGF-I, relative to insulin, and by alpha IR3. An 11-kb transcript characteristic of mRNA for the type 1 IGF receptor was recognized in poly(A+) RNA derived from cultured canine tracheal epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1990 Sep
PMID:Canine tracheal epithelial cells express the type 1 insulin-like growth factor receptor and proliferate in response to insulin-like growth factor I. 216 99

Lung cancer is a major health problem, with over 38,000 new cases expected every year in West Germany. A more complete understanding of the biology of lung cancer will hopefully lead to therapeutic modalities. The possible autocrine growth regulation in small-cell lung cancer and non-small-cell lung cancer has been demonstrated for bombesin/GRP, vasopressin, neurotensin, EGF/TGF alpha, transferrin-related peptides and insulin-like growth factors. This contribution concentrates on recent data concerning binding sites, growth promoting effects and secretion of IGFs in lung cancer cell lines. The production of IGF-binding proteins which were also produced by lung cancer cell lines modifies the autocrine/paracrine model for IGFs since then proteins can either enhance or inhibit the effect of IGFs on tumor growth.
J Steroid Biochem Mol Biol 1990 Dec 20
PMID:Growth regulation by insulin-like growth factors in lung cancer. 217 66

Trypanosoma cruzi amastigotes present receptors for human transferrin as indicated by the saturable binding of 125I-transferrin to this form of the parasite. Computerized Scatchard analysis revealed one class of receptors present at 8.1 X 10(4) receptors per amastigote with a Kd of 2.82 microM. Immunofluorescence studies indicate that more than 90% of amastigotes bind human transferrin, whereas trypomastigotes do not. Iron is required for amastigote growth in cell-free medium since deferoxamine, an iron chelator, inhibits amastigote growth. Amastigote growth is restored when deferoxamine is removed from the medium. 59Fe-transferrin, which bound to amastigotes at 4 degrees C for 1 h, was readily dissociated from the parasite surface upon treatment with acid. However, this treatment did not disrupt binding that occurred at 37 degrees C for 1 h. Amastigote growth in cell-free medium is inhibited in ferrotransferrin-depleted serum, and addition of ferrotransferrin but not apotransferrin restores parasite growth. Western blots of solubilized amastigote membranes probed with anti-human transferrin receptor antibody recognize a protein of 200 kDa. This protein is present on the amastigote cell surface; therefore, human transferrin seems to interact with a 200-kDa surface amastigote protein receptor. Iron, which is essential for amastigote growth, thus appears to be delivered to T. cruzi amastigotes by transferrin receptor-mediated endocytosis.
Mol Biochem Parasitol 1990 Jan 15
PMID:Trypanosoma cruzi receptors for human transferrin and their role. 218 49

Migration of epithelial cells to cover areas of injury is thought to be important in the repair process following airway insult. Insulin is reported to be a growth factor for bronchial epithelial cells, and growth factors have been known to be chemotactic for many types of cells. Thus, we hypothesized that insulin may be a chemoattractant for bronchial epithelial cells. To evaluate this, we prepared bronchial epithelial cells and measured their chemotactic activity toward insulin. Bronchial epithelial cells were isolated by overnight digestion with bacterial protease, filtered through 100-microns nitex mesh, and then cultured at 1 x 10(6) cells/ml in tissue culture dishes in medium 199 supplemented with transferrin, insulin, epidermal growth factor, hydrocortisone, antibiotics, and 10% FCS for 3 d. The cultured cells were rinsed twice to remove supplements, trypsinized and resuspended at 1 x 10(6) cells/ml in medium 199 without supplements, and used as the cell source for chemotaxis. Chemotactic activity of bronchial epithelial cells was measured by the blindwell chamber technique using 8-microns Nuclepore filter membranes coated with 0.1% gelatin. The cells were added to the top wells in a 48-multiwell chamber with insulin in the bottom wells and incubated for 6 h at 37 degrees C, 5% CO2. Bronchial epithelial cells migrated in response to insulin in a dose-dependent manner up to an optimal dose of insulin, 100 micrograms/ml, and decreased at higher concentrations. The number of migrated cells per 10 high power fields was 33.7 +/- 1.9 at the optimum and 3.7 +/- 0.7 without insulin (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1990 Jun
PMID:Bronchial epithelial cells respond to insulin and insulin-like growth factor-I as a chemoattractant. 218 58


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