期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 46, 期 11, 页码 1551-1557出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2009.03.009
关键词
Hypoxia; Hypoxia-inducible transcription factor; Metabolomics; Isoprostane; Altitude; Free radicals
资金
- Department of Surgery Academic Enrichment Funds
- Department of Anesthesiology
- Altitude Research Center, University of Colorado
- Merck Sharp Dohme
Hypoxia plays a crucial role in the pathogenesis of a multitude of diseases and clinical conditions such as cancer, diabetes, cardiovascular disease, stroke, pulmonary disease, inflammation, organ transplant, and wound healing. Investigations into the role of hypoxia-inducible transcription factor (HIF) in disease development have been conducted with the basic premise that HIF is activated in vivo during hypoxia in humans, yet this basic physiologic premise has never verified. Thus, we hypothesized that HIF-1 DNA binding would be enhanced in vivo in humans in response to acute global hypoxia. Fourteen human subjects were exposed to normoxia (1600 m) and hypoxia (4300 m, approximate to 12% O-2) in a hypobaric hypoxic chamber (8 h). HIF-1 DNA binding and HIF-1 alpha protein were evaluated in circulating leukocytes. Oxidative markers were evaluated by plasma metabolomics using nuclear magnetic resonance and by urinary 15-F-2t-isoprostane concentrations. Leukocyte HIF-1 DNA binding was increased (p=0.007) and HIF-1 alpha was greater during hypoxia compared to normoxia. Circulating total glutathione was reduced by 35% (p=0.001), anti lactate and succinate were increased by 29 and 158%, respectively (p=0.007 and 0.001), as were urinary 15-F-2t-isoprostanes (p=0.037). HIF-1 DNA binding and HIF-1 alpha, were elevated in vivo in leukocytes of healthy human Subjects exposed to 12% oxygen, in association with plasma and urinary markers of hypoxic stress. (C) 2009 Elsevier Inc. All rights reserved.
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