The Control of Hepatic Iron Uptake: Correlation with Transferrin Synthesis

Morton, A. G.

doi:10.1111/j.1365-2141.1978.tb03619.x

Cited by 19 publications

(9 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, in our study, we also observed an inverse correlation between iron and Tf concentrations in the serum of Tmprss6-ASO-treated mice, consistent with previous reports demonstrating a negative correlation between iron deficiency and Tf synthesis (56)(57)(58). Intriguingly, this suggests that increased serum Tf levels might be utilized as a parameter to predict iron deficiency and evaluate when Tmprss6-ASO treatment should be stopped.…”

Section: Figuresupporting

confidence: 78%

Reducing TMPRSS6 ameliorates hemochromatosis and β-thalassemia in mice

Guo¹,

Casu²,

Gardenghi³

et al. 2013

J. Clin. Invest.

206

196

View full text Add to dashboard Cite

.β-Thalassemia and HFE-related hemochromatosis are 2 of the most frequently inherited disorders worldwide. Both disorders are characterized by low levels of hepcidin (HAMP), the hormone that regulates iron absorption. As a consequence, patients affected by these disorders exhibit iron overload, which is the main cause of morbidity and mortality. HAMP expression is controlled by activation of the SMAD1,5,8/SMAD4 complex. TMPRSS6 is a serine protease that reduces SMAD activation and blocks HAMP expression. We identified second generation antisense oligonucleotides (ASOs) targeting mouse Tmprss6. ASO treatment in mice affected by hemochromatosis (Hfe -/-) significantly decreased serum iron, transferrin saturation and liver iron accumulation. Furthermore, ASO treatment of mice affected by β-thalassemia (HBB th3/+ mice, referred to here after as th3/+ mice) decreased the formation of insoluble membrane-bound globins, ROS, and apoptosis, and improved anemia. These animals also exhibited lower erythropoietin levels, a significant amelioration of ineffective erythropoiesis (IE) and splenomegaly, and an increase in total hemoglobin levels. These data suggest that ASOs targeting Tmprss6 could be beneficial in individuals with hemochromatosis, β-thalassemia, and related disorders.

show abstract

Section: Figuresupporting

confidence: 78%

Reducing TMPRSS6 ameliorates hemochromatosis and β-thalassemia in mice

Guo¹,

Casu²,

Gardenghi³

et al. 2013

J. Clin. Invest.

206

196

View full text Add to dashboard Cite

show abstract

“…Morton and Tavill (69,70) have used perfusion of rat liver to examine the effect of prior iron deficiency of the donor rat on transferrin synthesis by the perfused liver. They observed increased synthesis of transferrin which was attributed to lack of iron stored in the hepatocytes as ferritin.…”

Section: Regulation Of Receptor Functionmentioning

confidence: 99%

“…The integration of transferrin iron supply to the liver, the function of receptors and the role of ferritin as a receptacle for iron has received only desultory attention. Morton and Tavill (69,70) have used perfusion of rat liver to examine the effect of prior iron deficiency of the donor rat on transferrin synthesis by the perfused liver. They observed increased synthesis of transferrin which was attributed to lack of iron stored in the hepatocytes as ferritin.…”

Section: ) 'mentioning

confidence: 99%

Transferrin and Its Receptor: Their Roles in Cell Function

Bomford

Munro

1985

Hepatology

View full text Add to dashboard Cite

Transferrin, its receptor and the entry of iron into the cell have sprung into prominence because of recent evidence that proliferation of various cell types involves regulation of this sequence of events, as evidenced especially by changes in receptor number. A third component functionally linked to transferrin and its receptor is the intracellular iron-storage protein, ferritin, which ensures against toxic levels of free ferrous iron, which might otherwise cause peroxidative damage to cell membranes and other cell structures (1). In this article, we shall focus on interactions between these three proteins of iron exchange, their roles in homeostasis and especially their role in relation to the liver which is a major organ of iron storage.

show abstract

“…Liver iron uptake may involve the reversible binding of transferrin to specific receptor sites (Gardiner & Morgan, 1974) in a process similar to that in erythropoietic cells (Jandl & Katz, 1963) and placenta (Laurel1 & Morgan, 1964). Net transfer to the hepatocyte is related to the iron stores in the liver and may be regulated in part by the available storage capacity of apoferritin (Morton & Tavill, 1978). The regulation of liver iron mobilization is poorly understood.…”

mentioning

confidence: 99%

The Regulation of Iron Release from the Perfused Rat Liver

Baker¹,

Morton²

1980

Br J Haematol

Self Cite

View full text Add to dashboard Cite

Factors affecting iron efflux from the isolated perfused rat liver were studied following the intravenous administration of transferrin-(59)Fe or transferrin-(55)Fe administered to the rat from 1.5 h to 3.5 d before perfusion of the liver. The liver was perfused with rat red cells suspended either in rat plasma or Eagle's Basal Medium (EBM). The mean rate of efflux into a plasma pool containing normal iron and transferrin concentrations was 0.9% of the initial hepatic radioactive iron pool per hour. In EBM the average rate of efflux was 0.1%/h and this could be increased to the rate observed with plasma by the addition of apotransferrin. The rate of iron release from the liver in the presence of apotransferrin or other chelators was inversely proportional to the time of prelabelling. Maximal release rates were observed in livers perfused within 5 h of administering transferrin-(59)Fe to the rat. The effect of apotransferrin on efflux into EBM was concentration dependent. However, the maximum release of liver iron by apotransferrin occurred at physiological apotransferrin concentrations and addition of apotransferrin to plasma produced no increase in the rate of iron efflux. The stimulation of iron release in EBM caused by apotransferrin could be reversed by reducing the unsaturated iron binding capacity of the perfusate, either by addition of iron or removal of apotransferrin. However, increasing the iron concentration in the perfusate by the addition of iron-saturated transferrin without any reduction in the unsaturated iron binding capacity additionally increased iron release into plasma and EBM. This presumably reflects the exchange of plasma transferrin-(56)Fe for liver (59)Fe. Hence iron release measured in these studies represent the sum of two processes-net release of (59)Fe induced by apotransferrin and iron exchange between plasma and liver iron pools. Apotransferrin and desferrioxamine were equally effective, per unit iron binding capacity, in mobilizing liver iron, and may compete for the same parenchymal iron pool. This suggests that mobilization of iron by apotransferrin may depend solely on its ability to chelate ferric iron and not on a more specific ferroxidase activity or interaction with membrane receptors.

show abstract

The Control of Hepatic Iron Uptake: Correlation with Transferrin Synthesis

Cited by 19 publications

References 29 publications

Reducing TMPRSS6 ameliorates hemochromatosis and β-thalassemia in mice

Reducing TMPRSS6 ameliorates hemochromatosis and β-thalassemia in mice

Transferrin and Its Receptor: Their Roles in Cell Function

The Regulation of Iron Release from the Perfused Rat Liver

Contact Info

Product

Resources

About