Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10767583 | Biochemical and Biophysical Research Communications | 2007 | 7 Pages |
Abstract
Hypoxia-inducible factors (HIFs) are key mediators of cellular adaptation to hypoxia, but also respond to non-hypoxic stimuli. To clarify involvement in metabolic disturbances, HIFs were characterised in rats subjected to insulin-induced hypoglycaemia or cellular glucoprivation provoked by 2-deoxy-d-glucose (2-DG). Using real-time qPCR, organ-specific expression of HIF-1α, -2α, -3α, -1β, and of the target gene GLUT-1 was determined. Distribution of HIF-3α proteins was examined by immunohistochemistry. Both, insulin and 2-DG resulted in a widespread increase in HIF-3α mRNA. HIF-2α mRNA increased in lung and heart after 2-DG only, whereas other HIFs remained unaffected. A pronounced increase of protein levels in cerebral cortex was observed for HIF-3α. Functional significance of HIF induction was reflected in enhancement of GLUT-1 mRNA. Transcriptional up-regulation of HIF-3α represents a typical response to in vivo hypoglycaemia and glucoprivation. These data suggest an involvement of the HIF system in metabolic derangements as for instance caused by diabetes.
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Authors
Marc Heidbreder, Fatimunnisa Qadri, Olaf Jöhren, Andreas Dendorfer, Reinhard Depping, Frederike Fröhlich, Klaus F. Wagner, Peter Dominiak,