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

Adaptation to hypoxia is regulated by hypoxia-inducible factor 1 (HIF-1), a heterodimeric transcription factor consisting of an oxygen-regulated α subunit and a constitutively expressed β subunit. Although HIF-1 is regulated mainly by oxygen tension through the oxygen-dependent degradation of its α 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-1α 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-1α expression varies among different organs. In liver and kidney, HIF-1α reaches maximal levels after 1 h and gradually decreases to baseline levels after 4 h of continuous hypoxia. ...