The intravenous anesthetic propofol inhibits hypoxia-inducible factor 1 activity in an oxygen tension-dependent manner

Satoshi Takabuchi, Kiichi Hirota, Kenichiro Nishi, Seiko Oda, Tomoyuki Oda, Koh Shingu, Arimichi Takabayashi, Takehiko Adachi, Gregg L. Semenza, Kazuhiko Fukuda

Research output: Contribution to journalArticlepeer-review

Abstract

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-1α subunit under 20% or 5% O2 conditions, but not under 1% O2 conditions.

Original languageEnglish (US)
Pages (from-to)434-438
Number of pages5
JournalFEBS Letters
Volume577
Issue number3
DOIs
StatePublished - Nov 19 2004

Keywords

  • Hypoxia
  • Hypoxia-inducible factor 1
  • Prolyl hydroxylase
  • Propofol
  • Von Hippel-Lindau

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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