这是今日出版的Science上文章,做得很好,对研究低氧领域的会员有重要的参考意义。
Redistribution of Intracellular Oxygen in Hypoxia by Nitric Oxide: Effect on HIF1
Thilo Hagen,1 Cormac T. Taylor,2 Francis Lam,1 Salvador Moncada1*
Cells exposed to low oxygen concentrations respond by initiating defense mechanisms, including the stabilization of hypoxia-inducible factor (HIF) 1, 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 HIF1 during hypoxia. In studies of cultured cells, we show that this effect is a result of an increase in prolyl hydroxylase–dependent degradation of HIF1. 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.
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www.sciencemag.org/cgi/content/full/302/5652/1975/DC1
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