Hypoxia-inducible factor 1 levels vary exponentially over a physiologically relevant range of O2 tension
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Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric basic helix-loop-helix protein implicated in the transcriptional activation of genes encoding erythropoietin, glycolytic enzymes, and vascular endothelial growth factor in hypoxic mammalian cells. In this study, we have quantitated HIF-1 DNA-binding activity and protein levels of the HIF-1 alpha and HIF-1 beta subunits in human HeLa cells exposed to O2 concentrations ranging from 0 to 20% in the absence or presence of 1 mM KCN to inhibit oxidative phosphorylation and cellular O2 consumption. HIF-1 DNA-binding activity, HIF-1 alpha protein and HIF-1 beta protein each increased exponentially as cells were subjected to decreasing O2 concentrations, with a half maximal response between 1.5 and 2% O2 and a maximal response at 0.5% O2, both in the presence and absence of KCN. The HIF-1 response was greatest over O2 concentrations associated with ischemic/hypoxic events in vivo. These results provide evidence for the involvement of HIF-1 in O2 homeostasis and represent a functional characterization of the putative O2 sensor that initiates hypoxia signal transduction leading to HIF-1 expression.
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ROS are required to trigger the apoptotic mechanism.
“that ROS are required to trigger the apoptotic mechanism (68, 172, 207, 323)”
From Mitochondrial reactive oxygen species production in excitable cells: Modulators of mitochondrial and cell function (2009) · cites this paper as [172]
HIF-1 DNA-binding activity and concentrations of HIF-1α and HIF-1β proteins increase exponentially with decreasing O2 concentration in HeLa cells.
“The HIF‐1 DNA‐binding activity of cells and the concentrations of HIF‐1α and HIF‐1β proteins increased exponentially with decreasing O2 concentration.”
From Hypoxia signaling in cancer: Implications for therapeutic interventions (2023) · cites this paper as [23]
At a cellular level, hypoxia and hypoxic responses generally occur at a PO2 ≤ ~1 kPa (≤~7-10 mm Hg or ~1% O2).
“at a cellular level, hypoxia and hypoxic responses generally occur at a PO2 ≤ ~1 kPa (≤~7–10 mm Hg or ~1 % O2) [4].”
From Hypoxia and hypoxia-inducible factors as regulators of T cell development, differentiation, and function (2013) · cites this paper as [4]
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Quantitative design strategies for fine control of oxygen in microfluidic systems
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The role of adropin, HIF-1α and apelin biomarkers in the diagnosis of acute mesentaric ischemia
Kurt, E., Tekin, E., Kurt, N., & Bayramoglu, A. (2022) · The American Journal of Emergency Medicine · doi:10.1016/j.ajem.2021.10.058 · Cited by 13 · see citing works
- Authors
- Jiang, B. H., Semenza, G. L., Bauer, C., & Marti, H. H.
- Affiliations
- Johns Hopkins University (US)
- Venue
- American Journal of Physiology-Cell Physiology
- Publisher
- American Physiological Society
- Published
- 1996-10-01
- Volume
- 271
- Issue
- 4
- Pages
- C1172-C1180
- ISSN
- 0363-6143 (ISSN-L)
- 1522-1563
- OpenAlex
- W1937401270
- Cited by
- 1,213
- References
- 32
- Citations by year
- 2026: 12 · 2025: 22 · 2024: 22 · 2023: 23 · 2022: 30 · 2021: 47 · 2020: 26 · 2019: 34 · 2018: 29 · 2017: 30 · 2016: 46 · 2015: 47 · 2014: 32 · 2013: 51 · 2012: 50
- FWCI
- 11.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal of Physiology-Cell Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- Johns Hopkins University
- National Institutes of Health (5r01dk039869-16)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK39869)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Keywords
- HIF-1, HIF-1α, oxygen partial pressure, oxygen homeostasis, oxygen sensors, hypoxia signaling, DNA-binding activity, cyanide, oxidative phosphorylation inhibition, HeLa cells, hypoxia
- MeSH terms
- Cell Nucleus, DNA-Binding Proteins, HeLa Cells, Humans, Nuclear Proteins, Oxygen, Potassium Cyanide, Transcription Factors, Blotting, Western, Gene Expression, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit
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