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| Redistribution of intracellular oxygen in hypoxia by nitric oxide: Effect on HIF1 alpha |
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| Author(s): Hagen T, Taylor CT, Lam F, Moncada S |
| Source: SCIENCE Volume: 302 Issue: 5652 Pages: 1975-1978 Published: DEC 12 2003 |
| Times Cited: 256 References: 24 |
| Abstract: Cells exposed to low oxygen concentrations respond by initiating defense mechanisms, including the stabilization of hypoxia-inducible factor (HIF) 1alpha, 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 HIF1alpha during hypoxia. In studies of cultured cells, we show that this effect is a result of an increase in prolyl hydroxylase dependent degradation of HIF1alpha. 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Moncada, S (reprint author), UCL, Wolfson Inst Biomed Res, Gower St, London WC1E 6BT, England |
Addresses:
1. UCL, Wolfson Inst Biomed Res, London WC1E 6BT, England
2. Natl Univ Ireland Univ Coll Dublin, Conway Inst Biomed & Biochem Res, Dublin 4, Ireland |
| Publisher: AMER ASSOC ADVANCEMENT SCIENCE, 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: 752NL |
| ISSN: 0036-8075 |
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