Reversible inhibition of hypoxia‐inducible factor 1 activation by exposure of hypoxic cells to the volatile anesthetic halothane

FEBS Letters

Hirota, Kiichi¹  Semenza, Gregg L.²  Itoh, Tatsuya¹  Namba, Tsunehisa¹  Fukuda, Kazuhiko¹ 

[1] Department of Anesthesia, Kyoto University Hospital, Kyoto University, Kyoto 606-8507, Japan;Institute of Genetic Medicine, Department of Pediatrics and Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21287-3914, USA

关键词: Hypoxia-inducible factor 1;    Volatile anesthetic;    Halothane;    Gene expression;    HIF-1;    hypoxia-inducible factor 1;    HRE;    hypoxia-responsive element;    DFX;    desferrioxamine;    ENO1;    enolase 1;    VEGF;    vascular endothelial growth factor;    TAD;    transactivation domain;    VHL;    von Hippel–Lindau;   

DOI  :  10.1016/S0014-5793(01)03119-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 O₂ 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-1α protein accumulation and transcriptional activity at clinically relevant doses.

【 授权许可】

Unknown