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Hypoxia-inducible factor-1 alpha is regulated at the post-mRNA level
R H Wenger1, I Kvietikova, A Rolfs
1Institute of Physiology, University of Zürich-Irchel, Switzerland.
Kidney International
|February 1, 1997
Summary
Hypoxia-inducible factor-1 alpha (HIF-1 alpha) mRNA levels do not significantly change with oxygen levels. This suggests HIF-1 alpha is not regulated by transcription, despite its role in oxygen-regulated gene expression.
Area of Science:
- Molecular Biology
- Cellular Biology
- Gene Regulation
Background:
- Hypoxia-inducible factor-1 (HIF-1) regulates oxygen-sensitive genes like VEGF.
- HIF-1 is a heterodimer of HIF-1 alpha and HIF-1 beta subunits.
- Regulation of HIF-1 itself is not fully understood.
Purpose of the Study:
- To investigate the regulation of HIF-1 alpha under varying oxygen conditions.
- To determine if HIF-1 alpha mRNA levels correlate with HIF-1 DNA binding activity.
Main Methods:
- Detection of HIF-1 alpha mRNA in cell lines under normoxic and hypoxic conditions.
- Measurement of VEGF mRNA levels and HIF-1 DNA binding activity after hypoxic induction.
- Incubation of HeLaS3 cells in tonometers at different oxygen concentrations (20% O2 vs. 0.5% O2) for extended periods.
Main Results:
- HIF-1 alpha mRNA was detected under normoxic conditions, but no HIF-1 DNA binding activity was observed.
- Hypoxic induction increased VEGF mRNA and HIF-1 DNA binding activity, but HIF-1 alpha mRNA levels remained stable.
- No significant changes in HIF-1 alpha mRNA levels were found over time at different oxygen concentrations.
Conclusions:
- HIF-1 alpha mRNA levels do not appear to be transcriptionally regulated by oxygen levels.
- The regulation of HIF-1 DNA binding activity may not directly follow HIF-1 alpha mRNA kinetics.