Prolonged Hypoxia Differentially Regulates Hypoxia-inducible Factor (HIF)-1α and HIF-2α Expression in Lung Epithelial Cells

@article{Uchida2004ProlongedHD,
  title={Prolonged Hypoxia Differentially Regulates Hypoxia-inducible Factor (HIF)-1$\alpha$ and HIF-2$\alpha$ Expression in Lung Epithelial Cells},
  author={Tokujiro Uchida and Fabrice Rossignol and Michael A. Matthay and R{\'e}mi Mounier and Sylvianne Couette and Eric Clottes and Christine Cl{\'e}rici},
  journal={Journal of Biological Chemistry},
  year={2004},
  volume={279},
  pages={14871 - 14878}
}
Transcriptional adaptations to hypoxia are mediated by hypoxia-inducible factor (HIF)-1, a heterodimer of HIF-α and aryl hydrocarbon receptor nuclear translocator subunits. The HIF-1α and HIF-2α subunits both undergo rapid hypoxia-induced protein stabilization and bind identical target DNA sequences. When coexpressed in similar cell types, discriminating control mechanisms may exist for their regulation, explaining why HIF-1α and HIF-2α do not substitute during embryogenesis. We report that, in… 
View on ASBMB
jbc.org
341 Citations
Highly Influential Citations
8
Background Citations
95
Methods Citations
2
Results Citations
8

341 Citations

Citation Type

Citation Type

Hypoxia upregulates hypoxia inducible factor (HIF)-3α expression in lung epithelial cells: characterization and comparison with HIF-1α
TLDR
HIF-3α, as a member of the HIF system, is complementary rather than redundant to HIF-1α induction in protection against hypoxic damage in alveolar epithelial cells, according to a variety of activating or inhibitory pharmacological agents.
Cobalt stimulates HIF-1-dependent but inhibits HIF-2-dependent gene expression in liver cancer cells.
TLDR
HIF-1 and HIF-2 specific gene activating functions respond differently to different stimuli and suggest the operation of oxygen-independent and gene- or tissue-specific regulatory mechanisms involving additional transcription factors or co-activators.
Differential Hypoxic Regulation of Hypoxia-Inducible Factors 1α and 2α
TLDR
It is found that transcription of HIF-2α was consistently increased by hypoxia, whereas transcription ofHIF-1α showed variable levels of repression, suggesting an important role of Hif-2 α in the regulation of tumor progression under chronic hypoxic conditions.
Hypoxia-inducible factor-1β (HIF-1β) is upregulated in a HIF-1α-dependent manner in 518A2 human melanoma cells under hypoxic conditions.
TLDR
A Hen's egg test-chorioallantoic membrane model of angiogenesis and invasion indicated a local expression of HIF-1β and implies a biological relevance of these findings, which indicate a novel cell specific mechanism which might prevent Hif-1 β to become a limiting factor.
Regulation of the HIF-system in human macrophages--differential regulation of HIF-α subunits under sustained hypoxia.
TLDR
For the first time evidence is provided that ahif is regulated by the Hif-system and influences HIF-1α expression in primary human macrophages and it could be shown thatAhif indeed is able to modulate the hypoxic expression of HIF -1α and influences the expression of the H IF-target gene Enolase-2.
The hypoxia-associated factor switches cells from HIF-1α- to HIF-2α-dependent signaling promoting stem cell characteristics, aggressive tumor growth and invasion.
TLDR
HAF, by causing a switch from a HIF-1α- to Hif-2α-dependent response to hypoxia, provides a mechanism for more aggressive growth of tumors under prolongedhypoxia.
Hsp70 and CHIP Selectively Mediate Ubiquitination and Degradation of Hypoxia-inducible Factor (HIF)-1α but Not HIF-2α*
TLDR
Hsp70- and CHIP-dependent ubiquitination represents a molecular mechanism by which prolonged hypoxia selectively reduces the levels of Hif-1α but not HIF-2α protein.
Recruitment of HIF-1alpha and HIF-2alpha to common target genes is differentially regulated in neuroblastoma: HIF-2alpha promotes an aggressive phenotype.
TLDR
High HIF-2alpha protein levels were correlated with advanced clinical stage and high VEGF expression and predicted poor prognosis in a clinical neuroblastoma material and have general tumor biological implications.
REST mediates resolution of HIF-dependent gene expression in prolonged hypoxia
TLDR
It is hypothesized that REST represses transcription of Hif-1α in prolonged hypoxia, thus contributing to the resolution of the HIF-1 α response.
Stabilization of Hypoxia-inducible Factor-1α by Prostacyclin under Prolonged Hypoxia via Reducing Reactive Oxygen Species Level in Endothelial Cells*
TLDR
A novel function of PGI2 is demonstrated in down-regulating reactive oxygen species production by attenuating NADPH oxidase activity, which stabilizes HIF-1α in human umbilical vein endothelial cells exposed to prolonged hypoxia.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 37 REFERENCES
Differential Roles of Hypoxia-Inducible Factor 1α (HIF-1α) and HIF-2α in Hypoxic Gene Regulation
TLDR
It is demonstrated that HIF-2α does regulate a variety of broadly expressed hypoxia-inducible genes, suggesting that its function is not restricted, as initially thought, to endothelial cell-specific gene expression.
Up-regulation of hypoxia-inducible factors HIF-1α and HIF-2α under normoxic conditions in renal carcinoma cells by von Hippel-Lindau tumor suppressor gene loss of function
TLDR
Evidence is provided for a role of the VHL protein in regulation of angiogenesis and erythropoiesis mediated by the HIF-1α and Hif-2α proteins.
Hypoxia-inducible factor-1 alpha is regulated at the post-mRNA level.
TLDR
The hypoxia-inducible factor-1 (HIF-1) is involved in the induction of oxygen regulated genes such as erythropoietin and vascular endothelial growth factor (VEGF) and there was some variation in Hif-1 alpha mRNA levels, but there did not find significant changes over this time frame, suggesting that HIF- 1 alpha is not transcriptionally regulated.
Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension.
Hypoxia-inducible factor 1 (HIF-1) is found in mammalian cells cultured under reduced O2 tension and is necessary for transcriptional activation mediated by the erythropoietin gene enhancer in…
Predominant role of hypoxia-inducible transcription factor (Hif)-1alpha versus Hif-2alpha in regulation of the transcriptional response to hypoxia.
TLDR
Among a panel of hypoxia-inducible genes, responses were critically dependent on H if-1 alpha but not Hif-2 alpha in both endothelial and breast cancer cells but critically dependent in renal carcinoma cells.
RNA interference for HIF-1alpha inhibits its downstream signalling and affects cellular proliferation.
  • J. Hänze, B. Eul, +5 authors F. Rose
  • Biology, Medicine
    Biochemical and biophysical research communications
  • 2003
TLDR
This approach was found to suppress the shift from from S-phase to G1-phase observed in A549 cells in response to hypoxia, supporting a role of HIF-1alpha in oxygen-dependent cell cycle regulation.
Hypoxia rapidly activates HIF‐3α mRNA expression
TLDR
The results suggest that induction at the transcriptional level is a unique feature of HIF‐3α, which therefore may represent a rapidly reacting component of the HIF system in protection against hypoxic damage.
Cobalt Inhibits the Interaction between Hypoxia-inducible Factor-α and von Hippel-Lindau Protein by Direct Binding to Hypoxia-inducible Factor-α*
TLDR
These findings show that cobalt mimics hypoxia, at least in part, by occupying the VHL-binding domain of HIF-α and thereby preventing the degradation of Hif-α.
Induction of endothelial PAS domain protein-1 by hypoxia: characterization and comparison with hypoxia-inducible factor-1alpha.
TLDR
Functional studies in a mutant cell line expressing neither HIF-1alpha nor EPAS-1 confirmed that both proteins interact with hypoxically responsive targets, but suggest target specificity with greater EPas-1 transactivation of the VEGF promoter than the LDH-A promoter.
Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1 alpha.
TLDR
It is demonstrated that HIF-1alpha is a master regulator of cellular and developmental O2 homeostasis in Hif1a-/- embryos that manifested neural tube defects, cardiovascular malformations, and marked cell death within the cephalic mesenchyme.
...
1
2
3
4
...