PMID- 10594641
OWN - NLM
STAT- MEDLINE
DCOM- 20000210
LR  - 20190815
IS  - 0953-816X (Print)
IS  - 0953-816X (Linking)
VI  - 11
IP  - 12
DP  - 1999 Dec
TI  - Induction of hypoxia-inducible factor-1 (HIF-1) and its target genes following 
      focal ischaemia in rat brain.
PG  - 4159-70
AB  - HIF-1 is a heterodimeric transcription factor, induced by hypoxia, that is 
      composed of HIF-1alpha and HIF-1beta protein subunits. It binds to 
      promoter/enhancer elements and stimulates the transcription of hypoxia-inducible 
      target genes, including glucose transporter-1 and the glycolytic enzymes. Because 
      HIF-1 activation might promote cell survival in hypoxic tissues, we studied the 
      effect of permanent middle cerebral artery occlusion on the expression of 
      HIF-1alpha, HIF-1beta and several HIF-1 target genes in adult rat brain. After 
      focal ischaemia, mRNAs encoding HIF-1alpha, glucose transporter-1 and several 
      glycolytic enzymes were up-regulated in the peri-infarct penumbra. This was 
      observed by 7.5 h after the onset of ischaemia and increased further at 19 and 24 
      h. Regional cerebral blood flow was moderately decreased at 1 and 24 h after the 
      ischaemia in areas of HIF-1 and HIF-1 target gene induction. Because hypoxia 
      induces HIF-1 in other tissues, systemic hypoxia (6% O2 for 4.5 h) was also shown 
      to increase HIF-1alpha protein expression in the adult rat brain. It is proposed 
      that decreased blood flow to the penumbra decreases the supply of oxygen and that 
      this induces HIF-1 and its target genes. This is the first study to show 
      induction of HIF-1 after focal ischaemia in brain. Increased expression of HIF-1 
      target genes as a result of HIF-1 activation by hypoxia may contribute to tissue 
      viability in the hypoxic/ischaemic penumbra by increasing glucose transport and 
      glycolysis.
FAU - Bergeron, M
AU  - Bergeron M
AD  - Department of Neurology, University of California at San Francisco and Veterans 
      Affairs Medical Center, California 94121, USA.
FAU - Yu, A Y
AU  - Yu AY
FAU - Solway, K E
AU  - Solway KE
FAU - Semenza, G L
AU  - Semenza GL
FAU - Sharp, F R
AU  - Sharp FR
LA  - eng
GR  - HL55338/HL/NHLBI NIH HHS/United States
GR  - NS14543/NS/NINDS NIH HHS/United States
GR  - NS28167/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Hif1a protein, rat)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Animals
MH  - Brain/*metabolism
MH  - Cerebrovascular Circulation/physiology
MH  - DNA-Binding Proteins/biosynthesis/*genetics
MH  - *Gene Expression Regulation/physiology
MH  - Helix-Loop-Helix Motifs
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Hypoxia-Ischemia, Brain/etiology/*physiopathology
MH  - In Situ Hybridization
MH  - Infarction, Middle Cerebral Artery/complications/physiopathology
MH  - Male
MH  - Nuclear Proteins/biosynthesis/*genetics
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Transcription Factors/biosynthesis/genetics
MH  - Transcriptional Activation
MH  - Up-Regulation
EDAT- 1999/12/14 00:00
MHDA- 1999/12/14 00:01
CRDT- 1999/12/14 00:00
PHST- 1999/12/14 00:00 [pubmed]
PHST- 1999/12/14 00:01 [medline]
PHST- 1999/12/14 00:00 [entrez]
AID - ejn845 [pii]
AID - 10.1046/j.1460-9568.1999.00845.x [doi]
PST - ppublish
SO  - Eur J Neurosci. 1999 Dec;11(12):4159-70. doi: 10.1046/j.1460-9568.1999.00845.x.