Immunoelectron microscopic localization of hepatic transferrin receptors in human liver with and without iron overload

1988 ◽  
Vol 55 (1) ◽  
pp. 11-17 ◽  
Author(s):  
R. De Vos ◽  
R. Sciot ◽  
P. van Eyken ◽  
V. J. Desmet
2010 ◽  
Vol 57 (9) ◽  
pp. 2295-2303 ◽  
Author(s):  
M Marinelli ◽  
B Gianesin ◽  
M Balocco ◽  
P Beruto ◽  
C Bruzzone ◽  
...  

Author(s):  
Maosheng Xia ◽  
Wenzheng Guan ◽  
Ming Ji ◽  
Shuai Li ◽  
Zexiong Li ◽  
...  

ABSTRACTIron is the fundamental element for numerous physiological functions. Reduced ferrous (Fe2+) and oxidized ferric (Fe3+) are the two ionized iron states in the living organisms. In the cell membrane, divalent metal ion transporter 1 (DMT1) is responsible for cellular uptake of Fe2+, whereas transferrin receptors (TFR) carry transferrin (TF)-bound Fe3+. In this study we performed, for the first time, detailed analysis of the action of Fe ions on cytoplasmic free calcium ion concentration ([Ca2+]i) in astrocytes. Using qPCR and immunocytochemistry we identified DMT1 and TFR in astrocytes in primary cultures, in acutely isolated astrocytes and in brain tissue preparations; in situ both DMT1 and TFR are concentrated in astroglial perivascular endfeet. Administration of Fe2+ or Fe3+ in low μM concentrations evoked Ca2+ signals in astrocytes in vitro and in vivo. Iron ions triggered increase in [Ca2+]i by acting through two distinct molecular cascades. Uptake of Fe2+ by DMT1 inhibited astroglial Na+-K+-ATPase (NKA), which led to an elevation in cytoplasmic Na+ concentration (as measured by SBFI probe), thus reversing Na+/Ca2+ exchanger (NCX) thereby generating Ca2+ influx. Uptake of Fe3+ by TF-TFR stimulated phospholipase C to produce inositol 1,4,5-trisphosphate (InsP3), thus trigering InsP3 receptor-mediated Ca2+ release from the endoplasmic reticulum. Iron-induced Ca2+ signals promote astroglial release of arachidonic acid and prostaglandin E2 cytokines by activating cytosolic phospholipase A2 (cPLA2) and NF-κB signalling cascade. In summary, these findings reveal new mechanisms of iron-induced astrocytic signalling operational in conditions of iron overload, in response to which astrocytes actively accumulate excessive iron and activate neuroprotective pathways.


Author(s):  
F M J Zuyderhoudt ◽  
C Linthorst ◽  
G G A Jörning ◽  
N C J J Ladiges ◽  
A M Brugman

Ferritin was isolated from normal human liver and from iron-loaded human liver by gel chromatography and by ultracentrifugation. From each of these ferritin batches several isoferritin fractions were isolated by preparative isoelectric focusing. It was our aim to have at our disposal isoferritin fractions with relatively large pI ranges but distinctly different isoferritin profiles on analytical isoelectric focusing. These fractions were compared for their immunoreactivity. The total protein in the isoferritin fractions was measured by the nitrogen content. The immunoreactivity of the isoferritin fractions was measured as the ratio of the reaction in immunoassays to the nitrogen content of these fractions. We used radial immunodiffusion and enzyme-linked immunoassay to measure immunoreactivity. The immunoreactivity did not change obviously with the isoferritin composition of the isolated fractions. It is concluded that pathological changes in the isoferritin composition that might occur in liver ferritin during iron overload does not significantly influence the quantitative measurement of liver ferritin protein by immunological methods.


2019 ◽  
Vol 20 (9) ◽  
pp. 2132 ◽  
Author(s):  
Steven A. Bloomer ◽  
Kyle E. Brown

Iron is implicated in the pathogenesis of a number of human liver diseases. Hereditary hemochromatosis is the classical example of a liver disease caused by iron, but iron is commonly believed to contribute to the progression of other forms of chronic liver disease such as hepatitis C infection and nonalcoholic fatty liver disease. In this review, we present data from cell culture experiments, animal models, and clinical studies that address the hepatotoxicity of iron. These data demonstrate that iron overload is only weakly fibrogenic in animal models and rarely causes serious liver damage in humans, calling into question the concept that iron overload is an important cause of hepatotoxicity. In situations where iron is pathogenic, iron-induced liver damage may be potentiated by coexisting inflammation, with the resulting hepatocyte necrosis an important factor driving the fibrogenic response. Based on the foregoing evidence that iron is less hepatotoxic than is generally assumed, claims that assign a causal role to iron in liver injury in either animal models or human liver disease should be carefully evaluated.


1998 ◽  
Vol 44 (1) ◽  
pp. 40-44 ◽  
Author(s):  
Hlosukwazi Khumalo ◽  
Zvenyika A R Gomo ◽  
Victor M Moyo ◽  
Victor R Gordeuk ◽  
Thokozile Saungweme ◽  
...  

Abstract To test the hypothesis that the quantities of circulating transferrin receptors are reduced in iron overload, we studied serum transferrin receptors and indirect measures of iron status in 150 subjects from rural Zimbabwe. We found significant inverse correlations between serum concentrations of transferrin receptors and ferritin, the ratio of ferritin to aspartate aminotransferase, and transferrin saturation (r ≥0.44; P <0.001). The mean ± SD concentration of serum transferrin receptors in 23 subjects classified as having iron overload (ferritin >300 μg/L and transferrin saturation >60%) was 1.55 ± 0.61 mg/L, significantly lower than the 2.50 ± 0.62 mg/L in 75 subjects with normal iron stores (ferritin 20–300 μg/L and transferrin saturation 15–55%; P <0.0005) and the 2.83 ± 1.14 mg/L in 8 subjects with iron deficiency (ferritin <20 μg/L; P = 0.001). In keeping with the regulation of transferrin receptor expression at the cellular level, our findings suggest that serum transferrin receptors are decreased in the presence of iron overload.


2010 ◽  
Vol 44 (1) ◽  
pp. 28-33 ◽  
Author(s):  
Maja Chloupková ◽  
An-Sheng Zhang ◽  
Caroline A. Enns

2013 ◽  
Vol 1 (1) ◽  
pp. 5 ◽  
Author(s):  
Barbara Gianesin ◽  
Alessio Caminata ◽  
Piergiorgio Beruto ◽  
Francesco Romoli ◽  
Mauro Marinelli

2001 ◽  
Vol 120 (5) ◽  
pp. A565-A565
Author(s):  
J TALWALKAR ◽  
H TORGERSON ◽  
D BRANDHAGEN

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