Haem inhibits iron uptake subsequent to endocytosis of transferrin in reticulocytes

Abstract

Haem controls the rate of haem synthesis in erythroid cells by inhibiting iron incorporation from transferrin. The present results indicate that haem primarily inhibits the release of iron from transferrin subsequent to transferrin endocytosis and that the inhibition, of transferrin endocytosis caused by relatively high concentrations of haem is a secondary effect. Low concentrations of haem (10-25 ftM) significantly inhibit reticulocyte iron uptake and to a greater extent its incorporation into haem, but do not inhibit either the initial rate of transferrin uptake or its internalization by the cells.

Dimethyl sulphoxide and haemin induce ferrochelatase mRNA by different mechanisms in murine erythroleukaemia cells

“…Another important step in haemoglobin synthesis is iron uptake by erythroid cells (Ponka et ul, 1988). Haemin is known, however, to inhibit iron uptake subsequent to endocytosis of transferrin in reticulocytes (Ponka et al, 1988). Thus its positive effect on haemoglobin synthesis (Dabney & Beaudet, 1977) which is in part due to its incorporation into haemoglobin (Granick & Sassa,19 78), may also reflect its upregulation of FeC mRNA.…”

Human erythroid 5-aminolevulinate synthase: promoter analysis and identification of an iron-responsive element in the mRNA.

“…It can be envisaged that the amount of ALAS activity in differentiating erythroid cells is subject to at least two controls-mRNA levels will be increased by transcriptional activation of the ALAS gene through the action of erythropoietin but subsequent translation of this mRNA will be dependent on iron availability. There is evidence that iron uptake by erythroid cells limits the overall rate of heme synthesis (Gardner and Cox, 1988;Ponka et al, 1988). Hence, when iron enters the cell, translation of ALAS mRNA will be increased resulting in increased protoporphyrin production so that protoporphyrin formation is coupled to iron availability for subsequent heme formation.…”

“…During erythropoiesis, large amounts of heme are required for hemoglobin and there is evidence that ALAS catalyzes the rate-controlling step in heme formation (Bottomley and Miiller-Eberhard, 1988;Gardner and Cox, 1988;Ponka et al, 1988). As a first step towards understanding the molecular mechanisms modulating the expression of ALAS during erythroid cell differentiation, we have isolated cDNA clones and the gene for the human erythroid ALAS isozyme.…”

Ferrochelatase, glutathione peroxidase and transferrin receptor mRNA synthesis and levels in mouse erythroleukemia cells–mRNA synthesis and levels

“…Friend cells [ 161 is critical and rate-limiting for heme biosynthesis. They found that exogenous hemin inhibited transferrin iron utilization but not protoporphyrin synthesis [17] and that iron uptake was inhibited by hemin subsequent to the endocytosis of transfemn [18]. Fadigan and Dailey [ 191 obtained evidence that ferrochelatase or iron supply was rate-limiting for heme biosynthesis during the early stages of Friend cell differentiation.…”