Transferrin protein and iron uptake by cultured hepatocytes

Sibille, Jean-Claude; Octave, Jean‐Noël; Schneider, Yves‐Jacques; Trouet, André; Crichton, Robert R.

doi:10.1016/0014-5793(82)80769-2

Cited by 63 publications

(17 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It should also be mentioned that the data of Nunes et al [1 15] indicate that in their system fluid-phase endocytosis, as assessed by measuring accumulation of inulin, was approx. 10-fold higher than values reported by other investigators [34,48,117]. Furthermore, in the study of Nunes et al [115] the time course of iron uptake from transferrin was non-linear and the average rate of iron uptake could be calculated to approximately 50 pmol of Fe/h per 106 cells.…”

Section: Transferrin and Alcoholic Liver Diseasementioning

confidence: 66%

“…The effect depends on the concentration of transferrin and also on any additional effects of the weak base. For instance, methylamine raises the pH of endocytotic compartments containing FITC-transferrin but has no effect on hepatocyte iron uptake from transferrin [29] unless the concentration of transferrin is low [47,48]. By comparison, the weak base chloroquine which, in addition to its pH-raising effect, also inhibits the hepatocyte plasma membrane NADH: ferricyanide oxidoreductase, reduces hepatocyte iron uptake from transferrin by 45-50% regardless of the transferrin concentration [47].…”

Section: Thorstensen Unpublished Work)mentioning

confidence: 99%

“…The number of transferrin receptors on the hepatocyte plasma membrane is relatively few [7], and at 37°C cellular uptake of iron continues to increase when the extracellular concentration of transferrin is increased far in excess of the concentration needed to saturate all transferrin receptors [34,48,50,51]. This has led some investigators to conclude that adsorptive or fluidphase endocytosis is the main mechanism of hepatocyte uptake of iron from transferrin [48,50,51].…”

Section: Thorstensen Unpublished Work)mentioning

confidence: 99%

“…This has led some investigators to conclude that adsorptive or fluidphase endocytosis is the main mechanism of hepatocyte uptake of iron from transferrin [48,50,51]. Such mechanisms would involve a receptor-independent release of iron from transferrin.…”

Section: Thorstensen Unpublished Work)mentioning

confidence: 99%

See 3 more Smart Citations

The role of transferrin in the mechanism of cellular iron uptake

Thorstensen

Romslo

1990

Biochemical Journal

185

106

View full text Add to dashboard Cite

INTRODUCTIONThe role of transferrin and its cell surface receptor in cellular iron metabolism has received considerable interest during the last decade. Hence, over this period several reviews covering various aspects of the topic have been published.In this review we attempt to summarize the new knowledge and controversies encountered during the last 4-5 years. The focus is on iron metabolism by the hepatocyte. We also view the concept of transferrin-cell interactions from angles which previously may not have been given particular attention, and we include some aspects of iron metabolism not normally covered by reviews of this type. Central parts of what may be regarded as well-established knowledge either have been entirely omitted, or are only briefly described or mentioned to the extent considered relevant to the particular topic discussed. Important aspects of iron metabolism such as iron adsorption, haemochromatosis, ferritin iron and iron in infection and neoplasia are not covered in the present paper. Instead, the reader is referred to one or more of the recently published reviews [1-5] and references therein.

show abstract

Section: Transferrin and Alcoholic Liver Diseasementioning

confidence: 66%

Section: Thorstensen Unpublished Work)mentioning

confidence: 99%

Section: Thorstensen Unpublished Work)mentioning

confidence: 99%

Section: Thorstensen Unpublished Work)mentioning

confidence: 99%

See 2 more Smart Citations

The role of transferrin in the mechanism of cellular iron uptake

Thorstensen

Romslo

1990

Biochemical Journal

185

106

View full text Add to dashboard Cite

show abstract

“…Previously, the contribution made by pinocytosis to the hepatocyte iron uptake has been estimated as a small percentage of total iron uptake [19,201. This has been calculated from the uptake of [c~rboxyl-'~C]dextran [21], [3H]inulin [22], ['4C]sucrose [19] or '251-polyvinylpyrrolidone [12], and converting the uptake into equivalents of fluid internalized. This procedure has given estimates of pinocytosis in the range 0.2-0.4 p l k by lo6 cells, similar to that derived from contains the same concentration of diferric transferrin as the extracellular medium, the equivalent amount of iron internalized may be calculated.…”

Section: Resultsmentioning

confidence: 99%

The process of cellular uptake of iron from transferrin

Bakøy

Thorstensen

1994

European Journal of Biochemistry

View full text Add to dashboard Cite

In an attempt to improve our understanding of the complex interplay between cell compartments and chemical species during cellular uptake of iron from transfenin, we designed a computer simulation program based on current models of receptor-mediated endocytosis and pinocytosis. The program calculates and visualizes, as a function of time, the changes in transfenin, apotransferrin, and iron concentrations occurring in all relevant cellular compartments during cellular iron acquisition from transferrin. Simulation of literature data showed that the program generates results that are in accordance with experimental data. Furthermore, from measurements of the uptake of [carboxyl-''C]dextran we could utilize the program to suggest rate constants characteristic for the pinocytic process in rat reticulocytes. Moreover, simulations indicate that the apparent difference in the iron uptake process observed between reticulocytes and hepatocytes may be explained by the contribution made by pinocytosis to the iron uptake process. Finally, the present program should have potential as an educational tool during introduction to the field of receptor-mediated endocytosis in general and to cellular iron metabolism in particular.The mechanism of cellular uptake of iron from transfenin has been the matter of debate for several years. Two different views have crystallized, one favouring a plasma membrane redox process, the other advocating receptor-mediated endocytosis (RME) [1]. The RME model for transfenin-iron uptake includes the binding of transferrin to the cell surface transferrin receptor, the internalization of the transferrintransferrin-receptor complex into endosomes, the dissociation of iron from transferrin with the subsequent transport of iron into the cytosol, and the exocytosis and release of apotransferrin [2].Previously, several mathematical models have been developed for simulating the interaction between ligands and receptors (i.e. growth factors such as interferon, tumor necrosis factor, or epidermal growth factor) undergoing endocytosis [3-91. These models were mainly aimed at producing estimates of rate constants for the various parts of the RME process for these ligands.To the best of our knowledge, no single study has addressed the dynamic interplay between the different parts of the process of cellular uptake of iron from transfenin in its entirety.The aim of the present study was to combine current knowledge on the separate parts of the cellular transferriniron uptake process into a computer simulation program. other compartments. In this way, it would be possible to predict where and to what extent experimental manipulations would affect the process of cellular iron uptake from transferrin. Thus, the program will aid in the interpretation of experimental data, and in the planning of experiments. It will also serve as a tool to rapidly try out hypotheses which may be laborious to test at the laboratory bench.In the present paper we describe the development and function of a computer simulation program which...

show abstract

The mechanisms of iron uptake by fetal rat hepatocytes in culture

1986

View full text Add to dashboard Cite

The mechanisms of iron accumulation by cultured hepatocytes isolated from fetal rat liver (19 days gestation) were investigated using rat transferrin labeled with 125I and 59Fe. The rates of iron and transferrin internalization by the cells were measured by incubating the hepatocytes with the labeled transferrin at 37 degrees C followed by treatment with pronase at 4 degrees C to remove surface-bound transferrin and iron. Iron internalization increased linearly with time. Approximately 65% of the internalized iron was incorporated into ferritin. In contrast to iron, the rate of transferrin internalization was biphasic, with a rapid phase during the first 10 to 15 min and a second slower phase which becomes more apparent after that time. Iron and transferrin internalization were temperature-dependent. Chase experiments showed that the internalized transferrin donated all of its iron to the cell and was then released in a biphasic manner which was dependent on the time of preincubation with radiolabeled transferrin. These experiments showed that iron uptake occurs by at least three processes. The first mechanism involves the specific receptor-mediated endocytosis of transferrin. Each cell has an average of 7.8 +/- 1.0 X 10(5) (mean +/- SE, n = 5) transferrin binding sites with an apparent association constant of 2.0 +/- 0.4 X 10(6) M-1. The second process is nonsaturable up to a transferrin concentration of at least 6 microM but like the specific process, also leads to accumulation of iron in excess of transferrin. It involves the endocytosis of transferrin mediated by 4.2 X 2.6 X 10(5) M-1.(ABSTRACT TRUNCATED AT 250 WORDS)

show abstract

Transferrin protein and iron uptake by cultured hepatocytes

Cited by 63 publications

References 24 publications

The role of transferrin in the mechanism of cellular iron uptake

The role of transferrin in the mechanism of cellular iron uptake

The process of cellular uptake of iron from transferrin

The mechanisms of iron uptake by fetal rat hepatocytes in culture

Contact Info

Product

Resources

About