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• W2061636637 abstract "Summary. To determine whether erythropoietin (EPO) affects haem biosynthesis and iron transport, we studied the effects of EPO on the expression of erythroid 5‐aminolevulinate synthase (eALAS), ferrochelatase and divalent metal transporter 1 (DMT‐1) in human erythroid progenitor cells, and in the murine and human erythroid cell lines MEL and K562. Cytoplasmic e‐ALAS mRNA levels were significantly increased after incubation of cells with EPO for at least 24 h, which could be the result of a transcriptional mechanism. In contrast, ferrochelatase or DMT‐1 mRNA expression were not affected. Moreover, EPO also increased e‐ALAS enzyme activity after only 4 h of stimulation, when mRNA levels were unchanged. The underlying mechanism was an effect of EPO on e‐ALAS mRNA translation, which was under the control of iron regulatory proteins (IRP) 1 and 2. Thereby, EPO weakened the binding affinity of IRP‐2 to the iron responsive element (IRE) within e‐ALAS mRNA which resulted in the increased expression of e‐ALAS IRE‐controlled reporter gene constructs, following EPO stimulation. Our results show that EPO directly affected haem biosynthesis by stimulating the transcriptional and post‐transcriptional expression of the key enzyme e‐ALAS. These data provide new insights into the complex biochemical interaction between iron metabolism, haem biosynthesis and EPO biology." @default.
• W2061636637 created "2016-06-24" @default.
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• W2061636637 date "2002-07-25" @default.
• W2061636637 modified "2023-10-17" @default.
• W2061636637 title "Erythroid 5-aminolevulinate synthase, ferrochelatase and DMT1 expression in erythroid progenitors: differential pathways for erythropoietin and iron-dependent regulation" @default.
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• W2061636637 doi "https://doi.org/10.1046/j.1365-2141.2002.03626.x" @default.
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