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-1 alpha protein accumulation and transcriptional activity at clinically relevant doses. (C) 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.