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, and Kazuhiko Fukuda

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, and Kazuhiko Fukuda

FEBS Lettes, In press

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.

Posted: 火 - 10月 5, 2004 at 07:12 午後          

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