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Desferrioxamine induces erythropoietin gene expression and hypoxia- inducible factor 1 DNA-binding activity: implications for models of hypoxia signal transduction
Open accessAbstract
Erythropoietin (EPO) gene transcription is activated in kidney cells in vivo and in Hep3B cells exposed to hypoxia or cobalt chloride. Hypoxia- inducible factor 1 (HIF-1) is a nuclear factor that binds to the hypoxia-inducible enhancer of the EPO gene at a site that is required for transcriptional activation. HIF-1 DNA-binding activity is induced by hypoxia or cobalt chloride treatment of Hep3B cells. We report that treatment of Hep3B cells with desferrioxamine (DFX) induced HIF-1 activity and EPO RNA expression with kinetics similar to the induction of HIF-1 by hypoxia or cobalt chloride. Induction by each of these stimuli was inhibited by cycloheximide, indicating a requirement for de novo protein synthesis. DFX appears to induce HIF-1 by chelating iron as induction was inhibited by coadministration of ferrous ammonium sulfate. DFX administration to mice transiently increased EPO RNA levels in the kidney. As previously shown for hypoxia and cobalt treatment, DFX also induced HIF-1 activity in non-EPO-producing cells, suggesting the existence of a common hypoxia signal-transduction pathway leading to HIF-1 induction in different cell types.
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“HIF stabilization can be induced by iron chelators including desferrioxamine and bacterial siderophores [62, 63].”
From Hypoxia and hypoxia-inducible factors as regulators of T cell development, differentiation, and function (2013) · cites this paper as [62]
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Testa, U. (2008) · Springer eBooks · doi:10.1007/978-3-211-69459-6_1
Metadata
- Authors
- Wang, G., & Semenza, G.
- Affiliations
- Johns Hopkins University (US)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 1993-12-15
- Volume
- 82
- Issue
- 12
- Pages
- 3610-3615
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W1545825939
- Cited by
- 766
- References
- 33
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 12 · 2023: 24 · 2022: 18 · 2021: 26 · 2020: 24 · 2019: 18 · 2018: 19 · 2017: 17 · 2016: 34 · 2015: 24 · 2014: 26 · 2013: 26 · 2012: 32
- FWCI
- 5.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01dk039869-16)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 39869)
- Topics
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Hemoglobin structure and function
- Keywords
- deferoxamine, erythropoietin gene expression, HIF-1, iron chelation, cobalt chloride, Hep3B cells, ferrous ammonium sulfate, cycloheximide, de novo protein synthesis
- MeSH terms
- Base Sequence, Cell Line, Cell Nucleus, Cobalt, Deferoxamine, DNA-Binding Proteins, Erythropoietin, Humans, Liver Neoplasms, Molecular Sequence Data, Nuclear Proteins, RNA, Neoplasm, Transcription Factors, Tumor Cells, Cultured, Oligonucleotide Probes, Signal Transduction, Cell Hypoxia, Gene Expression, Hepatoblastoma, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit
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