Redistribution of Intracellular Oxygen in Hypoxia by Nitric Oxide: Effect on HIF1α

Cells exposed to low oxygen concentrations respond by initiating defense mechanisms, including the stabilization of hypoxia-inducible factor (HIF) 1α, a transcription factor that upregulates genes such as those involved in glycolysis and angiogenesis. Nitric oxide and other inhibitors of mitochondri...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2003-12, Vol.302 (5652), p.1975-1978
Main Authors: Hagen, Thilo, Taylor, Cormac T., Lam, Francis, Moncada, Salvador
Format: Article
Language:English
Subjects:
Biological and medical sciences
Cell lines
Cell metabolism, cell oxidation
Cell physiology
Distribution
Fundamental and applied biological sciences. Psychology
HEK293 cells
Hypoxia
Influence
Kidney cells
Molecular and cellular biology
Myotonic dystrophy
Nitric oxide
Oxygen
Proteins
Reactive oxygen species
Respiration
Western blotting
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Summary:Cells exposed to low oxygen concentrations respond by initiating defense mechanisms, including the stabilization of hypoxia-inducible factor (HIF) 1α, a transcription factor that upregulates genes such as those involved in glycolysis and angiogenesis. Nitric oxide and other inhibitors of mitochondrial respiration prevent the stabilization of HIF1α during hypoxia. In studies of cultured cells, we show that this effect is a result of an increase in prolyl hydroxylase-dependent degradation of HIF1α. With the use of Renilla luciferase to detect intracellular oxygen concentrations, we also demonstrate that, upon inhibition of mitochondrial respiration in hypoxia, oxygen is redistributed toward non-respiratory oxygen-dependent targets such as prolyl hydroxylases so that they do not register hypoxia. Thus, the signaling consequences of hypoxia may be profoundly modified by nitric oxide.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1088805