scholarly journals Transcriptional regulation by iron of the gene for the transferrin receptor.

1986 ◽  
Vol 6 (1) ◽  
pp. 236-240 ◽  
Author(s):  
K Rao ◽  
J B Harford ◽  
T Rouault ◽  
A McClelland ◽  
F H Ruddle ◽  
...  
Keyword(s):  
Transferrin Receptor ◽  
K562 Cells ◽  
Iron Chelator ◽  
Transcriptional Level ◽  
Transferrin Receptors ◽  
Intracellular Iron ◽  
Human Transferrin Receptor ◽  
Diferric Transferrin ◽  
Permeable Iron

Treatment of K562 cells with desferrioxamine, a permeable iron chelator, led to an increase in the number of transferrin receptors. Increasing intracellular iron levels by treatment of cells with either human diferric transferrin or hemin lowered the level of the transferrin receptors. By using a cDNA clone of the human transferrin receptor, we showed that the changes in the levels of the receptor by iron were accompanied by alterations in the levels of the mRNA for the receptor. The rapidity of these changes indicated that the mRNA had a very short half-life. By using an in vitro transcriptional assay with isolated nuclei, we obtained evidence that this regulation occurred at the transcriptional level.

Transcriptional regulation by iron of the gene for the transferrin receptor

1986 ◽  
Vol 6 (1) ◽  
pp. 236-240
Author(s):  
K Rao ◽  
J B Harford ◽  
T Rouault ◽  
A McClelland ◽  
F H Ruddle ◽  
...  
Keyword(s):  
Transferrin Receptor ◽  
K562 Cells ◽  
Iron Chelator ◽  
Transcriptional Level ◽  
Transferrin Receptors ◽  
Intracellular Iron ◽  
Human Transferrin Receptor ◽  
Diferric Transferrin ◽  
Permeable Iron

Treatment of K562 cells with desferrioxamine, a permeable iron chelator, led to an increase in the number of transferrin receptors. Increasing intracellular iron levels by treatment of cells with either human diferric transferrin or hemin lowered the level of the transferrin receptors. By using a cDNA clone of the human transferrin receptor, we showed that the changes in the levels of the receptor by iron were accompanied by alterations in the levels of the mRNA for the receptor. The rapidity of these changes indicated that the mRNA had a very short half-life. By using an in vitro transcriptional assay with isolated nuclei, we obtained evidence that this regulation occurred at the transcriptional level.

Effect of iron on transferrin receptor expression by human placental syncytiotrophoblast cells

1997 ◽  
Vol 9 (6) ◽  
pp. 609 ◽  
Author(s):  
Martha L. Kennedy ◽  
Gordon C. Douglas ◽  
Barry F. King
Keyword(s):  
Transferrin Receptor ◽  
Iron Status ◽  
Primary Cultures ◽  
Receptor Expression ◽  
Transferrin Receptors ◽  
Iron Salts ◽  
Intracellular Receptor ◽  
Cytotrophoblast Cells ◽  
Diferric Transferrin ◽  
Transferrin Receptor Expression

Transferrin receptor expression has been examined in primary cultures of morphologically differentiated placental syncytiotrophoblast cells. More than 90% of the cells were multinucleated. Incubation of syncytiotrophoblast for 4 days in the presence of iron salts had no effect on receptor expression assessed by measuring the binding of 125I-labelled transferrin. However, incubation of cells in the presence of human diferric transferrin (10-100 µM) led to a 50% decrease in surface and intracellular receptor expression. This down-regulation was not accompanied by a signicant decrease in receptor synthesis. In contrast to syncytiotrophoblast, expression of intracellular transferrin receptors in non-differentiated cytotrophoblast cells decreased when cells were cultured with iron salts; this was accompanied by decreased receptor synthesis. Addition of diferric transferrin to cytotrophoblast cells led to a 50% reduction in surface and intracellular receptor expression, similar to that seen in the syncytiotrophoblast. This reduction was accompanied by a decrease in receptor synthesis. In contrast to that of most cell types, the expression and distribution of trophoblast transferrin receptors were not altered by insulin, epidermal growth factor or hydrocortisone. These characteristics of syncytiotrophoblast transferrin receptor expression may assist in ensuring a supply of iron to the fetus regardless of the maternal iron status.

scholarly journals Regulation of heat shock protein synthesis by quercetin in human erythroleukaemia cells

1994 ◽  
Vol 300 (1) ◽  
pp. 201-209 ◽  
Author(s):  
G Elia ◽  
M G Santoro
Keyword(s):  
Heat Shock ◽  
Mammalian Cells ◽  
Elevated Temperatures ◽  
K562 Cells ◽  
Hsp70 Expression ◽  
Transcriptional Level ◽  
Hsp70 Mrna ◽  
Shock Proteins ◽  
Hsp70 Synthesis

Synthesis of heat-shock proteins (HSPs) is universally induced in eukaryotic and prokaryotic cells by exposure to elevated temperatures or to other types of environmental stress. In mammalian cells, HSPs belonging to the 70 kDa family (HSP70) have a regulatory role in several cellular processes, and have been shown to be involved in the control of cell proliferation and differentiation. Although many types of HSP70 inducers have been identified, only a few compounds, all belonging to the flavonoid group, have been shown to inhibit HSP70 induction. Because inhibitors of HSP70 synthesis could be an important tool with which to study the function of this protein, we have investigated the effect of quercetin, a flavonoid with antiproliferative activity which is widely distributed in nature, on HSP70 synthesis in human K562 erythroleukaemia cells after treatment with severe or mild heat shock and with other inducers. Quercetin was found to affect HSP70 synthesis at more than one level, depending on the conditions used. Indeed, after severe heat shock (45 degrees C for 20 min) treatment with quercetin, at non-toxic concentrations, was found to inhibit HSP70 synthesis for a period of 3-4 h. This block appeared to be exerted at the post-transcriptional level and to be cell-mediated, as the addition of quercetin during translation of HSP70 mRNA in vitro had no effect. After prolonged (90 min) exposure at 43 degrees C, however, quercetin was found to inhibit also HSP70 mRNA transcription. Pretreatment of K562 cells with quercetin had no effect on HSP70 expression, and quercetin needed to be present during induction to be effective. Under all conditions tested, the quercetin-induced block of HSP70 synthesis was found to be transient and, after an initial delay, synthesis of HSP70 reached the control rate and continued at the same level for several hours after the time at which HSP70 synthesis had been turned off in control cells. Finally, inhibition of HSP70 synthesis by quercetin appeared to be dependent on the temperature used and on the type of stressor.

scholarly journals A soluble form of the human transferrin receptor is released by activated lymphocytes in vitro

2008 ◽  
Vol 92 (3) ◽  
pp. 537-542 ◽  
Author(s):  
W. WOITH ◽  
I. NÜSSLEIN ◽  
C. ANTONI ◽  
D. I. DEJICA ◽  
T. H. WINKLER ◽  
...  
Keyword(s):  
Transferrin Receptor ◽  
Soluble Form ◽  
Activated Lymphocytes ◽  
Human Transferrin ◽  
Human Transferrin Receptor

scholarly journals Iterative endocytosis of transferrin by K562 cells

1994 ◽  
Vol 298 (1) ◽  
pp. 165-170 ◽  
Author(s):  
S P Young ◽  
A Bomford
Keyword(s):  
Cell Surface ◽  
Iron Uptake ◽  
Protein A ◽  
K562 Cells ◽  
Iron Chelator ◽  
Receptor Recycling ◽  
Weak Base ◽  
Uptake Process ◽  
The Difference ◽  
Diferric Transferrin

The effect of iron on the exocytosis of transferrin by K562 cells was studied by first allowing the cells to endocytose apotransferrin or diferric transferrin. Subsequent release of the apotransferrin was very rapid with a t 1/2 of 3.01 min, compared with 5.5 min for diferric transferrin. Release of apotransferrin was slowed by the weak base methylamine, t 1/2 8.0 min, but the effect of this agent was substantially greater when iron-transferrin was used, t 1/2 18.65 min, suggesting that methylamine affects both iron removal and receptor recycling. Release of iron-transferrin could be accelerated to a rate comparable with that of apotransferrin by addition of the permeant iron-chelator desferrioxamine. The difference in the rates of release of different forms of the protein could be explained by the re-endocytosis of the iron-rich protein, a process detected by the accelerated release of transferrin when the cells were washed in medium at pH 5.5 containing an iron-chelator or treated with a protease-containing medium to digest transferrin accessible at the cell surface. It appears that in cells incubated under control conditions, re-endocytosis of transferrin, which is incompletely depleted of iron, occurs and that a transferrin molecule may make two passes through the cell before all the iron is removed. This mechanism helps to explain why very little iron-transferrin is released from cells and why the efficiency of the iron uptake process is so high.

scholarly journals Synergistic inhibition of lymphoid tumor growth in vitro by combined treatment with the iron chelator deferoxamine and an immunoglobulin G monoclonal antibody against the transferrin receptor

Blood ◽  
1990 ◽  
Vol 76 (5) ◽  
pp. 991-995 ◽  
Author(s):  
JD Kemp ◽  
KM Smith ◽  
LJ Kanner ◽  
F Gomez ◽  
JA Thorson ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Immunoglobulin G ◽  
Transferrin Receptor ◽  
Picolinic Acid ◽  
Combined Treatment ◽  
Iron Chelator ◽  
Response Analysis ◽  
Synergistic Inhibition ◽  
Iron Chelator Deferoxamine

Abstract Data are presented indicating that the growth of 5 out of 5 murine lymphoid tumors can be inhibited in a synergistic fashion in vitro by combined treatment with the iron chelator deferoxamine (DFO) and an immunoglobulin G (IgG) monoclonal anti-transferrin receptor antibody (ATRA). A two-way dose/response analysis shows that the ATRA becomes more efficient as an inhibitor with increasing doses of DFO. Flow cytometric studies further support the view that IgG ATRAS impair transferrin receptor (TR) function by causing TR down-modulation and degradation, even when the presence of DFO acts to promote increased cell surface TR expression. It is also shown that an IgG ATRA is nearly as effective as an IgM ATRA in inhibiting tumor cell growth when used in combination with DFO. Finally, studies with the iron chelator picolinic acid show that it produces only additive, or very slightly supra-additive, effects when used in combination with the ATRA. Therefore, these studies not only continue to suggest that combination chelator/ATRA therapy warrants further investigation as a tool in the therapy of hematopoietic malignancies, but also make the following new points: (1) the clinically familiar iron chelator deferoxamine, but not all iron chelators, produces synergistic inhibition of tumor growth in vitro with ATRAS; and (2) IgG ATRAS, which may be clinically more attractive reagents than IgA or IgM ATRAS because of better access to extra vascular tissue spaces, have unexpectedly been found to function as powerful growth inhibitors when used in combination with DFO.

scholarly journals Acetaldehyde/alcohol dehydrogenase-2 (EhADH2) and clathrin are involved in internalization of human transferrin by Entamoeba histolytica

Microbiology ◽  
2011 ◽  
Vol 157 (1) ◽  
pp. 209-219 ◽  
Author(s):  
Magda Reyes-López ◽  
Rosa María Bermúdez-Cruz ◽  
Eva E. Avila ◽  
Mireya de la Garza
Keyword(s):  
Alcohol Dehydrogenase ◽  
Entamoeba Histolytica ◽  
Transferrin Receptor ◽  
Ferric Iron ◽  
Iron Ions ◽  
Coated Pits ◽  
Human Transferrin ◽  
Human Transferrin Receptor ◽  
Alcohol Dehydrogenase 2

Transferrin (Tf) is a host glycoprotein capable of binding two ferric-iron ions to become holotransferrin (holoTf), which transports iron in to all cells. Entamoeba histolytica is a parasitic protozoan able to use holoTf as a sole iron source in vitro. The mechanism by which this parasite scavenges iron from holoTf is unknown. An E. histolytica holoTf-binding protein (EhTfbp) was purified by using an anti-human transferrin receptor (TfR) monoclonal antibody. EhTfbp was identified by MS/MS analysis and database searches as E. histolytica acetaldehyde/alcohol dehydrogenase-2 (EhADH2), an iron-dependent enzyme. Both EhTfbp and EhADH2 bound holoTf and were recognized by the anti-human TfR antibody, indicating that they correspond to the same protein. It was found that the amoebae internalized holoTf through clathrin-coated pits, suggesting that holoTf endocytosis could be important for the parasite during colonization and invasion of the intestinal mucosa and liver.

scholarly journals Pharmacological iron-chelation as an assisted nutritional immunity strategy against Piscirickettsia salmonis infection

2020 ◽  
Vol 51 (1) ◽  
Author(s):  
Mario Caruffo ◽  
Dinka Mandakovic ◽  
Madelaine Mejías ◽  
Ignacio Chávez-Báez ◽  
Pablo Salgado ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Iron Chelation ◽  
Iron Chelator ◽  
Host Cells ◽  
Bacterial Disease ◽  
Protective Capacity ◽  
Intracellular Iron ◽  
Piscirickettsia Salmonis

Abstract Salmonid Rickettsial Septicaemia (SRS), caused by Piscirickettsia salmonis, is a severe bacterial disease in the Chilean salmon farming industry. Vaccines and antibiotics are the current strategies to fight SRS; however, the high frequency of new epizootic events confirms the need to develop new strategies to combat this disease. An innovative opportunity is perturbing the host pathways used by the microorganisms to replicate inside host cells through host-directed antimicrobial drugs (HDAD). Iron is a critical nutrient for P. salmonis infection; hence, the use of iron-chelators becomes an excellent alternative to be used as HDAD. The aim of this work was to use the iron chelator Deferiprone (DFP) as HDAD to treat SRS. Here, we describe the protective effect of the iron chelator DFP over P. salmonis infections at non-antibiotic concentrations, in bacterial challenges both in vitro and in vivo. At the cellular level, our results indicate that DFP reduced the intracellular iron content by 33.1% and P. salmonis relative load during bacterial infections by 78%. These findings were recapitulated in fish, where DFP reduced the mortality of rainbow trout challenged with P. salmonis in 34.9% compared to the non-treated group. This is the first report of the protective capacity of an iron chelator against infection in fish, becoming a potential effective host-directed therapy for SRS and other animals against ferrophilic pathogens.

scholarly journals Effect of aluminium on iron uptake and transferrin-receptor expression by human erythroleukaemia K562 cells

1990 ◽  
Vol 272 (2) ◽  
pp. 377-382 ◽  
Author(s):  
S J McGregor ◽  
M L Naves ◽  
R Oria ◽  
J K Vass ◽  
J H Brock
Keyword(s):  
Transferrin Receptor ◽  
Iron Uptake ◽  
K562 Cells ◽  
Inhibitory Effect ◽  
Receptor Expression ◽  
Transferrin Receptors ◽  
High Concentration ◽  
Intracellular Release ◽  
Aluminium Citrate ◽  
Transferrin Receptor Expression

Incubation of human erythroleukaemia K562 cells with Al-transferrin inhibited iron uptake from 59Fe-transferrin by about 80%. The inhibition was greater than that produced by a similar quantity of Fe-transferrin. Preincubation of cells for 6 h with either Al-transferrin or Fe-transferrin diminished the number of surface transferrin receptors by about 40% compared with cells preincubated with apo-transferrin. Al-transferrin did not compete significantly with Fe-transferrin for transferrin receptors and, when cells were preincubated for 15 min instead of 6 h, the inhibitory effect of Al-transferrin on receptor expression was lost. Both forms of transferrin also decreased the level of transferrin receptor mRNA by about 50%, suggesting a common regulatory mechanism. Aluminium citrate had no effect on iron uptake or transferrin-receptor expression. AlCl3 also had no effect on transferrin-receptor expression, but at high concentration it caused an increase in iron uptake by an unknown, possibly non-specific, mechanism. Neither Al-transferrin nor AlCl3 caused a significant change in cell proliferation. It is proposed that aluminium, when bound to transferrin, inhibits iron uptake partly by down-regulating transferrin-receptor expression and partly by interfering with intracellular release of iron from transferrin.

scholarly journals Synthetic Porcine Hepcidin Exhibits Different Roles in Escherichia coli and Salmonella Infections

2017 ◽  
Vol 61 (10) ◽  
Author(s):  
Dan Liu ◽  
Zhen-Shun Gan ◽  
Wan Ma ◽  
Hai-Tao Xiong ◽  
Yun-Qing Li ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Bacterial Infections ◽  
Iron Status ◽  
Iron Chelator ◽  
Intracellular Iron ◽  
Content Type ◽  
Defense Strategies ◽  
Salmonella Infections

ABSTRACT Hepcidin, an antimicrobial peptide, was discovered to integrate diverse signals from iron status and an infection threat and orchestrate a series of host-protective responses. Several studies have investigated the antimicrobial role of hepcidin, but the results have been controversial. Here, we aimed to examine the role of hepcidin in bacterial adherence and invasion in vitro. We found that porcine hepcidin could decrease the amount of the extracellular pathogen enterotoxigenic Escherichia coli (ETEC) K88 that adhered to cells because it caused the aggregation of the bacteria. However, addition of hepcidin to macrophages infected with the intracellular pathogen Salmonella enterica serovar Typhimurium enhanced the intracellular growth of the pathogen through the degradation of ferroportin, an iron export protein, and then the sequestration of intracellular iron. Intracellular iron was unavailable by use of the iron chelator deferiprone (DFO), which reduced intracellular bacterial growth. These results demonstrate that hepcidin exhibits different functions in extracellular and intracellular bacterial infections, which suggests that different defense strategies should be taken to prevent bacterial infection.

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