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