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 alpha subunit and a constitutively expressed beta subunit. Although HIF-1 is reg ulated mainly by oxygen tension through the oxygen-dependent degradation of its alpha subunit, in vitro it can also be modulated by cytokines, hormone s and genetic alterations. To investigate HIF-1 activation in vivo, we dete rmined the spatial and temporal distribution of HIF-1 in healthy mice subje cted to varying fractions of inspiratory oxygen. Immunohistochemical examin ation of brain, kidney, liver, heart, and skeletal muscle revealed that HIF -1 alpha is present in mice kept under normoxic conditions and is further i ncreased in response to systemic hypoxia. Moreover, immunoblot analysis sho wed that the kinetics of HIF-1 alpha expression varies among different orga ns. In liver and kidney, HIF-1 alpha reaches maximal levels after 1 h and g radually decreases to baseline levels after 4 h of continuous hypoxia. In t he brain, however, HIF-1 alpha is maximally expressed after 5 h and decline s to basal levels by 12 h. Whereas HIF-1 beta is constitutively expressed i n brain and kidney nuclear extracts, its hepatic expression increases conco mitantly with HIF-1 alpha. Overall, HIF-1 alpha expression in normoxic mice suggests that HIF-1 has an important role in tissue homeostasis.