The intravenous anesthetic propofol inhibits hypoxia-inducible factor 1 activity in an oxygen tension-dependent manner.
Hypoxia elicits a wide range of responses that occur at different organizational levels in the body. Hypoxia is not only a signal for energy conservation and metabolic change, but triggers expression of a select set of genes. The transcription factor hypoxia-inducible factor 1 (HIF-1) is now appreciated to be a master factor of the gene induction. Although knowledge on molecular mechanisms of HIF-1 activation in response to hypoxia is accumulating, the molecular mechanism of maintenance of HIF-1 activity under normoxic conditions remains to be elucidated. We demonstrate that the intravenous anesthetic propofol reversibly inhibits HIF-1 activity and the gene expression mediated by HIF-1 by blocking the synthesis of the HIF-1alpha subunit under 20% or 5% O2 conditions, but not under 1% O2 conditions.
Takabuchi
Satoshi
S
Department of Anesthesia, The Tazuke Kofukai Medical Research Institute, Kitano Hospital, 2-4-20, Ohgimachi, Kita-ku, Osaka 530-8480, Japan.
Hirota
Kiichi
K
Nishi
Kenichiro
K
Oda
Seiko
S
Oda
Tomoyuki
T
Shingu
Koh
K
Takabayashi
Arimichi
A
Adachi
Takehiko
T
Semenza
Gregg L
GL
Fukuda
Kazuhiko
K
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015687:Cell Hypoxia / Q000187:drug effects* / Q000235:genetics; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D015151:Immunoblotting; D007700:Kinetics; D008156:Luciferases / Q000378:metabolism; D009687:Nuclear Proteins / Q000187:drug effects*; D010100:Oxygen / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D015742:Propofol / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D014471:Umbilical Veins / Q000166:cytology
D018686:Anesthetics, Intravenous; D000911:Antibodies, Monoclonal; D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D008156:Luciferases; D005982:Glutathione Transferase; D010100:Oxygen; D015742:Propofol