Reversible inhibition of hypoxia-inducible factor 1 activation by exposure of hypoxic cells to the volatile anesthetic halothane.
Volatile anesthetics modulate a variety of physiological and pathophysiological responses including hypoxic responses. Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that mediates cellular and systemic homeostatic responses to reduced O(2) availability in mammals, including erythropoiesis, angiogenesis, and glycolysis. We demonstrate for the first time that the volatile anesthetic halothane blocks HIF-1 activity and downstream target gene expressions induced by hypoxia in the human hepatoma-derived cell line, Hep3B. Halothane reversibly blocks hypoxia-induced HIF-1alpha protein accumulation and transcriptional activity at clinically relevant doses.
Itoh
T
T
Department of Anesthesia, Kyoto University Hospital, Kyoto University, Kyoto 606-8507, Japan.
Namba
T
T
Fukuda
K
K
Semenza
G L
GL
Hirota
K
K
D000693:Anaerobiosis; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D003035:Cobalt / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006221:Halothane / Q000494:pharmacology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014157:Transcription Factors / Q000187:drug effects*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D018685:Anesthetics, Inhalation; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014157:Transcription Factors; D003035:Cobalt; C018021:cobaltous chloride; D003676:Deferoxamine; D006221:Halothane