The transcription factor HIF-1α plays a critical role in the growth factor-dependent regulation of both aerobic and anaerobic glycolysis
The transcription factor HIF-1α plays a critical role in the growth factor-dependent regulation of both aerobic and anaerobic glycolysis
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DOI：
10.1101/gad.1529107
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发表时间：
2007-05-01
影响因子：
10.5
通讯作者：
Thompson, Craig B.
中科院分区：
文献类型：
--
作者：
Lum, Julian J.;Bui, Thi;Thompson, Craig B.
哺乳动物细胞被认为具有一种细胞固有的能力，可以在缺氧时增加葡萄糖代谢。在这里，我们表明，造血细胞在低氧条件下上调厌氧糖酵解的能力依赖于受体介导的信号转导。在缺乏生长因子信号的情况下，造血细胞不能表达低氧诱导转录因子(Hif-1α)mRNA。缺乏生长因子的造血细胞不参与葡萄糖依赖的合成，既不表达Hif-1αmRNA，也不需要HIF-1α蛋白来调节细胞在低氧条件下的存活。然而，HIF-1α适用于生长因子刺激的细胞的生存，因为抑制HIF-1α会导致生长细胞暴露在低氧中时死亡。生长因子依赖的HIF-1α表达重新编程葡萄糖在细胞内的命运，导致葡萄糖依赖的合成减少和乳酸产生增加，当缺氧稳定HIF-1α蛋白时，这种作用增强。综上所述，这些数据表明，即使在没有缺氧的情况下，HIF-1α也有助于调节生长因子刺激的葡萄糖代谢。
Mammalian cells are believed to have a cell-intrinsic ability to increase glucose metabolism in response to hypoxia. Here we show that the ability of hematopoietic cells to up-regulate anaerobic glycolysis in response to hypoxia is dependent on receptor-mediated signal transduction. In the absence of growth factor signaling, hematopoietic cells fail to express hypoxia-inducible transcription factor (Hif-1 alpha) mRNA. Growth factor-deprived hematopoietic cells do not engage in glucose-dependent anabolic synthesis and neither express Hif-1 alpha mRNA nor require HIF-1 alpha protein to regulate cell survival in response to hypoxia. However, HIF-1 alpha is adaptive for the survival of growth factor-stimulated cells, as suppression of HIF-1 alpha results in death when growing cells are exposed to hypoxia. Growth factor-dependent HIF-1 alpha expression reprograms the intracellular fate of glucose, resulting in decreased glucose-dependent anabolic synthesis and increased lactate production, an effect that is enhanced when HIF-1 alpha protein is stabilized by hypoxia. Together, these data suggest that HIF-1 alpha contributes to the regulation of growth factor-stimulated glucose metabolism even in the absence of hypoxia.