Journal
GENES & DEVELOPMENT
Volume 21, Issue 9, Pages 1037-1049Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.1529107
Keywords
HIF-1 alpha; hypoxia; growth factor signaling; glucose metabolism; cell survival
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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.
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