HIF‐1 is expressed in normoxic tissue and displays an organ‐specific regulation under systemic hypoxia
By D. Stroka, Tobias Burkhardt, I. Desbaillets, Roland H. Wenger, D. Neil, C. Bauer, M. Gassmann, D. Candinas. The FASEB Journal, 2001
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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. Immunohisto‐chemical examination of brain, kidney, liver, heart, and skeletal muscle revealed that HIF‐1α is present in mice kept under normoxic conditions and is further in‐creased in response to systemic hypoxia. Moreover, immunoblot analysis showed that the kinetics of HIF‐1 α expression varies among different organs. In liver and kidney, HIF‐1 α reaches maximal levels after1hand gradually decreases to baseline levels after4hof continuous hypoxia. In the brain, however, HIF‐1α is maximally expressed after 5 h and declines to basal levels by 12 h. Whereas HIF‐1 β is constitutively expressed in brain and kidney nuclear extracts, its hepatic expression increases concomitantly with HIF‐1 α. Overall, HIF‐1 α 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. FASEB J. 15, 2445–2453 (2001)
Subfields: Cancer Research, Physiology
View Paper: https://www.semanticscholar.org/paper/8927ed9a0469f509f8673d90b68b6803a20c20e4
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Citations in the corpus
- Cellular adaptation to hypoxia: O2‐sensing protein hydroxylases, hypoxia‐inducible transcription factors, and O2‐regulated gene expression (2002, background): “verse normoxic organs within distinct cell types (43),”
- Differentiating the functional role of hypoxia‐inducible factor (HIF)‐1α and HIF‐2α (EPAS‐1) by the use of RNA interference: erythropoietin is a HIF‐2α target gene in Hep3B and Kelly cells (2004, background): “The two HIFα subunits, HIF-1α and HIF-2α, are widely, but in vivo, at least at the protein level, differentially expressed (5, 6).”
- Effects of short-term copper exposure on gill structure, metallothionein and hypoxia-inducible factor-1α (HIF-1α) levels in rainbow trout (Oncorhynchus mykiss) (2004, background): “Mice liver, kidney and brain cells (Stroka et al., 2001) and human lung epithelium (Uchida et al.”