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Stroka, D M; Burkhardt, T; Desbaillets, I; Wenger, R H; Neil, D A; Bauer, C; Gassmann, M; Candinas, D (2001). HIF-1 is expressed in normoxic tissue and displays an organ-specific regulation under systemic hypoxia. FASEB Journal, 15(13):2445-2453.

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Abstract

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.

Item Type:Journal Article, refereed
Communities & Collections:04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology
DDC:570 Life sciences; biology
Language:English
Date:2001
Deposited On:11 Feb 2008 12:23
Last Modified:28 Nov 2013 00:50
Publisher:Federation of American Societies for Experimental Biology
ISSN:0892-6638
Publisher DOI:10.1096/fj.01-0125com
PubMed ID:11689469
Citations:Web of Science®. Times Cited: 79
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