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

Deborah Stroka, Tobias Burkhard, I Debaillets, RH Wenger, Desley Neil, C Bauer, M Gassmann, Daniel Candinas

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)2445-2453
Number of pages9
JournalFASEB Journal
Volume15
DOIs
Publication statusPublished - 1 Oct 2002

Keywords

  • tissue hypoxia
  • hypoxia-inducible factor 1
  • ARNT

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