Hypoxia-inducible factor 1 levels vary exponentially over a physiologically relevant range of O2 tension

BH Jiang, GL Semenza, C Bauer… - American Journal of …, 1996 - journals.physiology.org
BH Jiang, GL Semenza, C Bauer, HH Marti
American Journal of Physiology-Cell Physiology, 1996journals.physiology.org
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 O2 concentrations ranging from 0 to
20% in the absence or presence of 1 mM KCN to inhibit oxidative phosphorylation and …
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 O2 concentrations ranging from 0 to 20% in the absence or presence of 1 mM KCN to inhibit oxidative phosphorylation and cellular O2 consumption. HIF-1 DNA-binding activity, HIF-1 alpha protein and HIF-1 beta protein each increased exponentially as cells were subjected to decreasing O2 concentrations, with a half maximal response between 1.5 and 2% O2 and a maximal response at 0.5% O2, both in the presence and absence of KCN. The HIF-1 response was greatest over O2 concentrations associated with ischemic/hypoxic events in vivo. These results provide evidence for the involvement of HIF-1 in O2 homeostasis and represent a functional characterization of the putative O2 sensor that initiates hypoxia signal transduction leading to HIF-1 expression.
American Physiological Society