Hypoxia-inducible factor 1 levels vary exponentially over a physiologically relevant range of O-2 tension
Hypoxia-inducible factor 1 levels vary exponentially over a physiologically relevant range of O-2 tension
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DOI：
10.1152/ajpcell.1996.271.4.c1172
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发表时间：
1996-10-01
影响因子：
5.5
通讯作者：
Marti, HH
中科院分区：
文献类型：
--
作者：
Jiang, BH;Semenza, GL;Marti, HH
低氧诱导因子1（HIF-1）是一种杂二型碱基 - 环螺旋蛋白，与编码促红细胞生成素，糖酵解酶和血管内皮生长因子的转录激活有关低氧哺乳动物细胞的转录激活。在这项研究中，我们已经定量HIF-1 DNA结合活性以及HIF-1α和HIF-1β亚基的蛋白质水平，在不存在或存在的情况下暴露于O-2浓度范围为0至20％的O-2浓度。 1 mM KCN的抑制氧化磷酸化和细胞O-2消耗。 HIF-1 DNA结合活性，HIF-1α蛋白和HIF-1β蛋白各异都会呈指数呈指数增加，因为细胞的浓度降低，其半马量响应在1.5至2％O-2之间，A在存在和不存在KCN的情况下，最大响应在0.5％O-2处。在体内与缺血/低氧事件相关的O-2浓度上，HIF-1反应最大。这些结果为HIF-1参与O-2稳态提供了证据，并代表了推定的O-2传感器的功能表征，该传感器启动了缺氧信号转导导致HIF-1表达。
Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric basic helix-loop-helix protein implicated in the transcriptional activation of genes encoding erythropoietin, glycolytic enzymes, and vascular endothelial growth factor in hypoxic mammalian cells. In this study, we have quantitated HIF-1 DNA-binding activity and protein levels of the HIF-1 alpha and HIF-1 beta subunits in human HeLa cells exposed to O-2 concentrations ranging from 0 to 20% in the absence or presence of 1 mM KCN to inhibit oxidative phosphorylation and cellular O-2 consumption. HIF-1 DNA-binding activity, HIF-1 alpha protein, and HIF-1 beta protein each increased exponentially as cells were subjected to decreasing O-2 concentrations, with a half-maximal response between 1.5 and 2% O-2 and a maximal response at 0.5% O-2, both in the presence and absence of KCN. The HIF-1 response was greatest over O-2 concentra tions associated with ischemic/hypoxic events in vivo. These results provide evidence for the involvement of HIF-1 in O-2 homeostasis and represent a functional characterization of the putative O-2 sensor that initiates hypoxia signal transduction leading to HIF-1 expression.