Abstract:
:The hypoxia-inducible factor 1alpha (HIF-1alpha), a member of the PAS superfamily, is a global regulator of cellular and systemic O(2) homeostasis as well as embryonic development. As the activity of HIF-1alpha is increased by a lowered oxygen tension in vivo and in vitro, we established a cell line producing high amounts of HIF-1alpha under normoxic conditions. As this overexpression was inducible by doxycycline, we can now provide a system to study HIF-1alpha-dependent gene regulation under normoxic as well as hypoxic conditions. We were able to show that the doxycycline-induced induction of the target gene HIF-1alpha--followed by the message of its target genes erythropoietin and vascular endothelial growth factor--is a dose- and time-dependent process. As the inducible overexpression of HIF-1alpha did not increase the rate of apoptosis, it provides a helpful new tool in drug discovery and tumor research to differentiate between hypoxia-dependent and hypoxia-independent pathways during HIF-1alpha-dependent gene regulation and HIF-1alpha-dependent effects on apoptosis.
journal_name
Pharmacologyjournal_title
Pharmacologyauthors
Meissner U,Allabauer I,Repp R,Rascher W,Dötsch Jdoi
10.1159/000072359subject
Has Abstractpub_date
2003-10-01 00:00:00pages
74-8issue
2eissn
0031-7012issn
1423-0313pii
72359journal_volume
69pub_type
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