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

Bing Hua Jiang, Gregg L. Semenza, Christian Bauer, Hugo H. Marti

Research output: Contribution to journalArticle

Abstract

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-1α and HIF-1β 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-1α protein, and HIF-1β 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.

Original languageEnglish (US)
Pages (from-to)C1172-C1180
JournalAmerican Journal of Physiology - Cell Physiology
Volume271
Issue number4 40-4
DOIs
StatePublished - Oct 1996

Keywords

  • cell hypoxia
  • gene expression
  • homeostasis
  • oxygen sensing
  • transcriptional regulation

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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