Hagen 2003 Science
Hagen T, Taylor CT, Lam F, Moncada S (2003) Redistribution of intracellular oxygen in hypoxia by nitric oxide: effect on HIF1alpha. Science 302(5652):1975-8. |
Hagen T, Taylor CT, Lam F, Moncada S (2003) Science
Abstract: Cells exposed to low oxygen concentrations respond by initiating defense mechanisms, including the stabilization of hypoxia-inducible factor (HIF) 1Ξ±, 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 HIF1Ξ± during hypoxia. In studies of cultured cells, we show that this effect is a result of an increase in prolyl hydroxylaseβdependent degradation of HIF1Ξ±. 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 nonrespiratory 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. β’ Keywords: Hypoxia, HIF, hydroxylases, nitric oxide β’ Bioblast editor: Sobotka O
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Stress:Oxidative stress;RONS, Hypoxia