HIF-1 is expressed in normoxic tissue and displays an organ-specific regulation under systemic hypoxia

FASEB J. 2001 Nov;15(13):2445-53. doi: 10.1096/fj.01-0125com.


Adaptation to hypoxia is regulated by hypoxia-inducible factor 1 (HIF-1), a heterodimeric transcription factor consisting of an oxygen-regulated alpha subunit and a constitutively expressed beta subunit. Although HIF-1 is regulated mainly by oxygen tension through the oxygen-dependent degradation of its alpha subunit, in vitro it can also be modulated by cytokines, hormones and genetic alterations. To investigate HIF-1 activation in vivo, we determined the spatial and temporal distribution of HIF-1 in healthy mice subjected to varying fractions of inspiratory oxygen. Immunohistochemical examination of brain, kidney, liver, heart, and skeletal muscle revealed that HIF-1alpha is present in mice kept under normoxic conditions and is further increased in response to systemic hypoxia. Moreover, immunoblot analysis showed that the kinetics of HIF-1alpha expression varies among different organs. In liver and kidney, HIF-1alpha reaches maximal levels after 1 h and gradually decreases to baseline levels after 4 h of continuous hypoxia. In the brain, however, HIF-1alpha is maximally expressed after 5 h and declines to basal levels by 12 h. Whereas HIF-1beta is constitutively expressed in brain and kidney nuclear extracts, its hepatic expression increases concomitantly with HIF-1alpha. Overall, HIF-1alpha expression in normoxic mice suggests that HIF-1 has an important role in tissue homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Cell Nucleus / chemistry
  • Cell Nucleus / drug effects
  • Cytoplasm / chemistry
  • Cytoplasm / drug effects
  • DNA-Binding Proteins / drug effects
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Dose-Response Relationship, Drug
  • Erythropoietin / blood
  • Female
  • Gene Expression Regulation / drug effects
  • Hypoxia / physiopathology*
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Immunoblotting
  • Immunohistochemistry
  • Kidney / drug effects
  • Kidney / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Nuclear Proteins / drug effects
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Oxygen / pharmacology
  • RNA, Messenger / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Time Factors
  • Tissue Distribution
  • Transcription Factors*


  • DNA-Binding Proteins
  • Hif1a protein, mouse
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Nuclear Proteins
  • RNA, Messenger
  • Transcription Factors
  • Erythropoietin
  • Oxygen