Hypoxia-inducible factor-1 alpha is regulated at the post-mRNA level

Kidney Int. 1997 Feb;51(2):560-3. doi: 10.1038/ki.1997.79.

Abstract

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). HIF-1 is a heterodimeric transcription factor consisting of an alpha and a beta subunit. The question of how HIF-1 itself is regulated remains to be elucidated. Studies performed in human Hep3B hepatoma cells suggested that the prevalent mode of HIF-1 action is an increase in HIF-1 alpha steady-state mRNA and protein levels after hypoxic exposure. In contrast to the reported very low basal HIF-1 alpha mRNA levels, however, we detected HIF-1 alpha mRNA in several cell lines cultured under normoxic conditions, although no HIF-1 DNA binding activity was observed. Following hypoxic induction, VEGF mRNA levels and HIF-1 DNA binding activity increased, but HIF-1 alpha mRNA levels remained largely unchanged. One possible explanation for this discrepancy might be that HIF-1 DNA binding activity does not follow HIF-1 alpha mRNA kinetics. We therefore incubated HeLaS3 cells in tonometers for 7.5 minutes up to four hours at either 20% O2 or 0.5% O2. Although there was some variation in HIF-1 alpha mRNA levels, we did not find significant changes over this time frame, suggesting that HIF-1 alpha is not transcriptionally regulated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Hypoxia / genetics
  • Cell Hypoxia / physiology
  • Cell Line
  • DNA / metabolism
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism*
  • Endothelial Growth Factors / genetics
  • Humans
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Kinetics
  • Lymphokines / genetics
  • Mice
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism*
  • RNA Processing, Post-Transcriptional
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • Transcription Factors*
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • DNA-Binding Proteins
  • Endothelial Growth Factors
  • HIF1A protein, human
  • Hif1a protein, mouse
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Lymphokines
  • Nuclear Proteins
  • RNA, Messenger
  • Transcription Factors
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • DNA