Hypoxia-inducible factor-1 alpha is regulated at the post-mRNA level.
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.
Wenger
R H
RH
Institute of Physiology, University of Zürich-Irchel, Switzerland.
Kvietikova
I
I
Rolfs
A
A
Gassmann
M
M
Marti
H H
HH
D000818:Animals; D015687:Cell Hypoxia / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D016228:Endothelial Growth Factors / Q000235:genetics; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007700:Kinetics; D008222:Lymphokines / Q000235:genetics; D051379:Mice; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D004268:DNA-Binding Proteins; D016228:Endothelial Growth Factors; C497442:HIF1A protein, human; C497443:Hif1a protein, mouse; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008222:Lymphokines; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D004247:DNA