Cited by 766Erythropoietin and Anemia TreatmentCancer, Hypoxia, and MetabolismHemoglobin structure and function

Desferrioxamine induces erythropoietin gene expression and hypoxia- inducible factor 1 DNA-binding activity: implications for models of hypoxia signal transduction

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Wang, GL, Semenza, GL·1993·Blood

Abstract

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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Crossref · 10.1182/blood.v82.12.3610.3610

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Authors
Wang, G., & Semenza, G.
Affiliations
Johns Hopkins University (US)
Venue
Blood
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
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 › Cell Biology › 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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