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The intravenous anesthetic propofol inhibits hypoxia‐inducible factor 1 activity in an oxygen tension‐dependent manner
Author(s) -
Takabuchi Satoshi,
Hirota Kiichi,
Nishi Kenichiro,
Oda Seiko,
Oda Tomoyuki,
Shingu Koh,
Takabayashi Arimichi,
Adachi Takehiko,
Semenza Gregg L.,
Fukuda Kazuhiko
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.10.042
Subject(s) - hypoxia inducible factor 1 , hypoxia (environmental) , anesthetic , propofol , transcription factor , oxygen tension , hypoxia inducible factors , chemistry , protein subunit , gene , pharmacology , oxygen , biology , anesthesia , medicine , biochemistry , organic chemistry
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% O 2 conditions, but not under 1% O 2 conditions.