Intracellular heme coordinately modulates globin chain synthesis, transferrin receptor number, and ferritin content in differentiating Friend erythroleukemia cells
Abstract
The effect of succinylacetone (SA), a highly specific inhibitor of ALA- dehydratase and heme synthesis, on hemoglobin (Hb) production, transferrin receptor (TfR), and ferritin expression was analyzed in differentiating Friend leukemia cells (FLC). This compound exerted a pronounced inhibitory effect not only on heme and Hb synthesis, but also on all the remaining above-mentioned parameters. In particular, SA induced: (1) a reduction of the level of alpha-globin mRNA; (2) a decreased number of exposed TfR molecules, without modification of their affinity for the ligand; (3) a reduced level of TfR RNA, without significant change of TfR gene transcription rate; and (4) a lower ferritin content. The addition of exogenous hemin to differentiating FLC exerted opposite effects, and particularly induced an increase of both the number of TfRs and ferritin content. These findings suggest that in erythroid cells optimal heme synthesis is required to coordinately sustain globin chains synthesis and TfR/ferritin production; thus, the intracellular heme level may represent a key regulatory factor in the Hb synthesis pathway.
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Ferritin mRNA induction was observed during DMSO- or hemin-induced differentiation of mouse Friend leukemia cells and hemin-mediated differentiation of K562 human chronic myelogenous leukemia cells.
“Ferritin mRNA induction was observed during DMSO-or hemin-induced differentiation of mouse Friend leukemia cells (FLC) and hemin-mediated differentiation of K562 human chronic myelogenous leukemia cells (17, 143, 194).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [17]
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- Authors
- Battistini, A., Coccia, E., Marziali, G., Bulgarini, D., Scalzo, S., Fiorucci, G., Romeo, G., Affabris, E., Testa, U., & Rossi, G.
- Affiliations
- Istituto Superiore di Sanità (IT)
- Department of Virology and Hematology, Istituto Superiore di Sanita, Rome, Italy.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 1991-10-15
- Volume
- 78
- Issue
- 8
- Pages
- 2098-2103
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2407050949
- Cited by
- 26
- References
- 48
- Citations by year
- 2026: 1
- FWCI
- 1.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Keywords
- heme biosynthesis, succinylacetone, alpha-globin mRNA, transferrin receptor, ferritin, hemoglobin synthesis, erythroid differentiation, Friend erythroleukemia cells, hemin
- MeSH terms
- Cell Differentiation, Dimethyl Sulfoxide, Leukemia, Erythroblastic, Acute, Ferritins, Globins, Heme, Heptanoates, Humans, Receptors, Transferrin
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