TY - JOUR
T1 - Non-hypoxic induction of HIF-3α by 2-deoxy-d-glucose and insulin
AU - Heidbreder, Marc
AU - Qadri, Fatimunnisa
AU - Jöhren, Olaf
AU - Dendorfer, Andreas
AU - Depping, Reinhard
AU - Fröhlich, Frederike
AU - Wagner, Klaus F.
AU - Dominiak, Peter
PY - 2007/1/12
Y1 - 2007/1/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33751536082&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2006.11.027
DO - 10.1016/j.bbrc.2006.11.027
M3 - Journal articles
C2 - 17125738
AN - SCOPUS:33751536082
SN - 0006-291X
VL - 352
SP - 437
EP - 443
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -
