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

作者：Deborah Stroka, Tobias Burkhardt, Isabelle Desbaillets, Roland H. Wenger, Desley Neil, Christian J. E. Bauer, MAX GASSMANN, Daniel Candinas · 发表于：The FASEB Journal · 年份：2001 · DOI：10.1096/fj.01-0125com · 被引用次数：722 · 研究领域：Cancer, Hypoxia, and Metabolism、Adenosine and Purinergic Signaling、Nitric Oxide and Endothelin Effects

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.