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,12,1,
* Liver Laboratories, University of Birmingham, Birmingham, UK;
Institutes of Physiology, University of Zürich, Zürich, Switzerland; and
Medical University Lübeck, Lübeck, Germany
2Correspondence: Liver Laboratories, Clinical Research Block, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, UK. E-mail: d.m.stroka{at}bham.ac.uk.
Adaptation to hypoxia is regulated by hypoxia-inducible factor 1 (HIF-1), a heterodimeric transcription factor consisting of an oxygen-regulated 
subunit and a constitutively expressed ß subunit. Although HIF-1 is regulated mainly by oxygen tension through the oxygen-dependent degradation of its 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-1 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-1 expression varies among different organs. In liver and kidney, HIF-1 reaches maximal levels after 1 h and gradually decreases to baseline levels after 4 h of continuous hypoxia. In the brain, however, HIF-1 is maximally expressed after 5 h and declines to basal levels by 12 h. Whereas HIF-1ß is constitutively expressed in brain and kidney nuclear extracts, its hepatic expression increases concomitantly with HIF-1. Overall, HIF-1 expression in normoxic mice suggests that HIF-1 has an important role in tissue homeostasis.—Stroka, D. M., Burkhardt, T., Desbaillets, I., Wenger, R. H., Neil, D. A. H., Bauer, C., Gassmann, M., Candinas, D. HIF-1 is expressed in normoxic tissue and displays an organ specific regulation under systemic hypoxia.
Key Words: hypoxia-inducible factor 1 • ARNT • tissue hypoxia
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