Reduced hepatic iron uptake from rat aglycotransferrin

1991 ◽  
Vol 4 (2) ◽  
pp. 90-94 ◽  
Author(s):  
Wei-Li Hu ◽  
Paul A. Chindemi ◽  
Erwin Regoeczi
Keyword(s):  
Iron Uptake ◽  
Hepatic Iron

Importance of Anemia and Transferrin Levels in the Regulation of Intestinal Iron Absorption in Hypotransferrinemic Mice

Blood ◽  
1999 ◽  
Vol 94 (9) ◽  
pp. 3185-3192 ◽  
Author(s):  
K.B. Raja ◽  
D.J. Pountney ◽  
R.J. Simpson ◽  
T.J. Peters
Keyword(s):  
Mutant Strain ◽  
Intestinal Mucosa ◽  
Iron Uptake ◽  
Iron Absorption ◽  
Total Iron ◽  
Hepatic Iron ◽  
Short Term ◽  
Liver Iron ◽  
Intestinal Iron Absorption ◽  
Per Se

The hypotransferrinemic mouse (trf hpx) is a mutant strain exhibiting transferrin deficiency, marked anemia, hyperabsorption of iron, and elevated hepatic iron stores. We set out to investigate the relative roles of anemia and of transferrin in the malregulation of intestinal iron absorption in these animals. Transfusion of erythrocytes obtained from littermate controls increased hemoglobin levels and reduced reticulocyte counts in recipient animals. Although mucosal to carcass 59Fe transfer was reduced, total duodenal iron uptake was not significantly affected. Iron absorption in homozygotes, in contrast to littermate controls, was not reduced by hyperoxia. Mouse transferrin injections, in the short term, increased delivery of iron to the marrow and raised hemoglobin levels. Although mucosal transfer and total iron uptake were reduced at the higher transferrin doses, total uptake was still higher than in controls. Daily injections of mouse/human transferrin for 3 weeks from weaning, normalized hemoglobin values, and markedly reduced liver iron and intestinal iron absorption values in trf hpxanimals. When such daily-injected mice were left for a week to allow transferrin clearance, iron absorption values were significantly enhanced; hemoglobin or hepatic iron levels were, however, not significantly altered. These data indicate that hyperabsorption of iron in trf hpx mice is not solely because of the anemia; transferrin levels per se do affect iron absorption, possibly via a direct effect on the intestinal mucosa.

166 Oxidative stress mediates hepatic iron uptake and

Hepatology ◽  
2003 ◽  
Vol 38 ◽  
pp. 235-235
Author(s):  
S HEGEDUSCH ◽  
J MANGIN ◽  
D ROST ◽  
A WELKER ◽  
K PANTOPOULOS ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Iron Uptake ◽  
Hepatic Iron

Preferential hepatic uptake of iron from rat asialotransferrin: possible engagement of two receptors

1986 ◽  
Vol 251 (3) ◽  
pp. G398-G404
Author(s):  
J. R. Rudolph ◽  
E. Regoeczi ◽  
P. A. Chindemi ◽  
M. T. Debanne
Keyword(s):  
Transferrin Receptor ◽  
Iron Uptake ◽  
Rat Hepatocytes ◽  
Hepatic Uptake ◽  
Hepatic Iron ◽  
Transferrin Receptors ◽  
Binding Studies ◽  
Human Transferrin ◽  
Homologous Protein ◽  
Intact Rats

Hepatic iron uptake from and degradation of rat asialotransferrin prepared from the least anionic (major) component of rat transferrin were studied in intact rats. In experiments lasting 60-90 min, rat asialotransferrin delivered a three to four times larger fraction of the Fe dose to the liver than rat transferrin. Variations in the concentration of endogenous circulating rat 2Fe-transferrin by up to 300% failed to affect the enhanced hepatic delivery of Fe from rat asialotransferrin. However, pretreating the animals with a large dose of asialomucin, or fully sialylated human transferrin, or a combination of both did affect the delivery. In all cases, rat asialotransferrin delivered Fe to the liver at rates comparable with those seen with rat transferrin. The reason for the efficacy of human transferrin was clarified in competitive binding studies on rat hepatocytes and reticulocytes, which showed that human transferrin possessed an approximately sevenfold higher affinity for rat transferrin receptors than the homologous protein. These findings suggest that the enhanced hepatic uptake of Fe from rat asialotransferrin is mediated by simultaneous binding of the ligand both through its glycan and transferrin receptor affinity site. Pretreatment with asialomucin and human transferrin had no suppressing effect on basal hepatic delivery of iron from rat 2Fe-transferrin. The data suggest that deposition of a significant fraction of Fe in rat liver from rat transferrin is likely to take place by a mechanism not involving transferrin receptors. Desialylation shortened the metabolic half-life of rat transferrin from 33 to 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of DMT1 Mutations at Birth and in the First Years of Life.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3586-3586
Author(s):  
Iolascon Achille ◽  
d’Apolito Maria ◽  
Servedio Veronica ◽  
De Falco Luigia ◽  
Piga Antonio ◽  
...  
Keyword(s):  
Iron Overload ◽  
Iron Uptake ◽  
Iron Absorption ◽  
Transferrin Saturation ◽  
Adult Life ◽  
Microcytic Anemia ◽  
Hepatic Iron ◽  
Liver Iron ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter

Abstract Divalent metal transporter 1 (DMT1) is involved in dietary iron uptake on the luminal side of duodenal enterocytes and transfers iron from the endosome to the cytosol in the marrow erythroblasts. Spontaneous (mk mice and Belgrade rats) or acquired (DMT1 -/- mice) inactivation of DMT1 in rodents produces a severe microcytic anemia at birth, caused by inefficient intestinal iron absorption and defective iron utilization in erythroid cells. The first reported patient with DMT1 mutations had microcytic anemia and iron overload in adult life. We here report the hematological phenotype of a newborn with a severe mycrocytic anemia (Hb 4 g/dL, MCV 71 fL) at birth and during the first months of life. Serum iron, transferrin saturation and serum ferritin were 160 microg/L, 100% and 846 ng/ml respectively at 3 months of age. Hepatic iron overload wad documented at the age of 5 years by both non invasive SQUID and liver biopsy. Sequence analysis of genomic DNA of the family revealed that the child was compound heterozygote for two novel DMT1 mutations, inherited by the asymptomatic parents. The first change deleted 3 bp (c.310 - 3_5del CTT) in intron 4 resulting in a splicing abnormality and the skipping of exon 5. The second was C>T 1246 substitution that causes arginine > cysteine replacement at position 416 (p. R416C) in the protein. This missense affects an highly conserved residue in one of the putative transmembrane domains. A striking reduction of the protein in peripheral blood cells of the proband was demonstrated by western blot using an anti-DMT1 antibody. The child required blood transfusions at birth and in the first two months of life. Thereafter, treatment with subcutaneous erythropoietin mantained hemoglobin levels between 7.5–9.5 g/dL, allowing transfusion-independence. The haematological phenotype of this patient highlights the essential role of DMT1 in erythropoiesis. The early and significant hepatic iron accumulation indicates that, as in animal models, DMT1 is dispensable for liver iron uptake. Finally DMT1 inactivation in the gut is likely bypassed by other pathways of iron absorption.

Importance of Anemia and Transferrin Levels in the Regulation of Intestinal Iron Absorption in Hypotransferrinemic Mice

Blood ◽  
1999 ◽  
Vol 94 (9) ◽  
pp. 3185-3192 ◽  
Author(s):  
K.B. Raja ◽  
D.J. Pountney ◽  
R.J. Simpson ◽  
T.J. Peters
Keyword(s):  
Mutant Strain ◽  
Intestinal Mucosa ◽  
Iron Uptake ◽  
Iron Absorption ◽  
Total Iron ◽  
Hepatic Iron ◽  
Short Term ◽  
Liver Iron ◽  
Intestinal Iron Absorption ◽  
Per Se

Abstract The hypotransferrinemic mouse (trf hpx) is a mutant strain exhibiting transferrin deficiency, marked anemia, hyperabsorption of iron, and elevated hepatic iron stores. We set out to investigate the relative roles of anemia and of transferrin in the malregulation of intestinal iron absorption in these animals. Transfusion of erythrocytes obtained from littermate controls increased hemoglobin levels and reduced reticulocyte counts in recipient animals. Although mucosal to carcass 59Fe transfer was reduced, total duodenal iron uptake was not significantly affected. Iron absorption in homozygotes, in contrast to littermate controls, was not reduced by hyperoxia. Mouse transferrin injections, in the short term, increased delivery of iron to the marrow and raised hemoglobin levels. Although mucosal transfer and total iron uptake were reduced at the higher transferrin doses, total uptake was still higher than in controls. Daily injections of mouse/human transferrin for 3 weeks from weaning, normalized hemoglobin values, and markedly reduced liver iron and intestinal iron absorption values in trf hpxanimals. When such daily-injected mice were left for a week to allow transferrin clearance, iron absorption values were significantly enhanced; hemoglobin or hepatic iron levels were, however, not significantly altered. These data indicate that hyperabsorption of iron in trf hpx mice is not solely because of the anemia; transferrin levels per se do affect iron absorption, possibly via a direct effect on the intestinal mucosa.

Lactoferrin interferes with uptake of iron from transferrin and asialotransferrin by the rat liver

1993 ◽  
Vol 264 (1) ◽  
pp. G112-G117
Author(s):  
W. L. Hu ◽  
E. Regoeczi ◽  
P. A. Chindemi ◽  
M. Bolyos
Keyword(s):  
Heparan Sulfate ◽  
Iron Uptake ◽  
Heparan Sulfate Proteoglycan ◽  
Hepatic Iron ◽  
Sulfate Proteoglycan ◽  
Charged Amino Acids ◽  
Negative Effect ◽  
Rat Livers ◽  
Dose Dependent ◽  
Positively Charged

Intravenous injection of bovine or human lactoferrin (6.25 x 10(-2) mumol/100 g body wt) in rats resulted in marked reduction of hepatic iron uptake from transferrin and asialotransferrin. The effect was dose dependent, saturable at approximately 5 mg/100 g body wt, and independent of lactoferrin's iron content. At this dose level, iron uptake from transferrin was reduced by 28% and from asialotransferrin by 43% in experiments lasting 90 min. Bovine lactoperoxidase, another basic protein, was similarly effective. The clearance of asialofetuin and pinocytosis of polyvinylpyrrolidone remained unaffected. Perfusion of isolated rat livers at 4 degrees C showed a strong reduction in asialotransferrin binding in the presence of lactoferrin. Chromatography of hepatic heparan sulfate proteoglycan on immobilized lactoferrin, lactoperoxidase, asialotransferrin, and transferrin showed that it possessed affinity for each of these proteins, more for the first two than the latter two. Heparan sulfate proteoglycan binding and efficacy in reducing hepatic iron uptake were also studied after selective modifications of positively charged amino acids in these proteins. The data obtained are compatible with the hypothesis that lactoferrin and other proteins with similarly high affinity for hepatic heparan sulfate exert their negative effect on iron uptake by preventing transferrin binding to the proteoglycan. The possibility is thus raised that the large number of low-affinity transferrin binding sites reported by earlier investigators for the liver may be heparan sulfate molecules.

Hepatic Iron Uptake in Treated Haemochromatosis

1977 ◽  
Vol 53 (3) ◽  
pp. 14P-14P
Author(s):  
R. Batey ◽  
J. Pettit ◽  
A. W. Nicholas ◽  
S. Sherlock
Keyword(s):  
Iron Uptake ◽  
Hepatic Iron

scholarly journals Hepatic Iron Uptake in Alcoholic Liver Disease

1983 ◽  
Vol 84 (1) ◽  
pp. 143-147 ◽  
Author(s):  
R.W. Chapman ◽  
Marsha Y. Morgan ◽  
R. Bell ◽  
Sheila Sherlock
Keyword(s):  
Liver Disease ◽  
Alcoholic Liver Disease ◽  
Iron Uptake ◽  
Hepatic Iron
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