PMID- 12117547
OWN - NLM
STAT- MEDLINE
DCOM- 20021106
LR  - 20190826
IS  - 0169-328X (Print)
IS  - 0169-328X (Linking)
VI  - 104
IP  - 1
DP  - 2002 Jul 15
TI  - Hypoxia-induced cell death and changes in hypoxia-inducible factor-1 activity in 
      PC12 cells upon exposure to nerve growth factor.
PG  - 21-30
AB  - The transcription factor hypoxia-inducible factor-1 (HIF-1) strongly contributes 
      to the expression of adaptive genes under hypoxic conditions. In addition, HIF-1 
      has been implicated in the regulation of delayed neuronal cell death. 
      Suspension-grown and adherent PC12 cells treated with NGF were used as an 
      experimental model for studying the relationship between hypoxia-induced cell 
      death and activation of HIF-1. Cell damage was assessed by flow cytometry of 
      double-stained (Annexin V and propidiumiodide) cells, and by analysis of the 
      overall death parameters LDH and mitochondrial dehydrogenase. In parallel, cells 
      were transfected with a control and a three-hypoxia-responsive-elements 
      (HRE)-containing vector and HIF-1-driven luciferase activity was determined. 
      Exposure of NGF-treated PC12 cells to hypoxia resulted in a higher cell death 
      rate when compared to untreated controls. PC12 cells exposed for 2 days to NGF 
      exhibited a decrease of HIF-1 activity up to a factor of ten. This decrease may 
      contribute to the enhanced hypoxia-induced cell death via reduced expression of 
      HIF-1alpha-regulated genes responsible for adaptation to hypoxia, like those for 
      glucose transport proteins and enzymes of the glycolytic chain. The decrease in 
      HIF-1 activity and the increase in hypoxia sensitivity may suggest that NGF act 
      as an hierarchically organized signaling molecule.
FAU - Charlier, Nico
AU  - Charlier N
AD  - Department of Neonatology, Charite, Humboldt University, 14057, Berlin, Germany.
FAU - Leclere, Norbert
AU  - Leclere N
FAU - Felderhoff, Ursula
AU  - Felderhoff U
FAU - Heldt, Julia
AU  - Heldt J
FAU - Kietzmann, Thomas
AU  - Kietzmann T
FAU - Obladen, Michael
AU  - Obladen M
FAU - Gross, Johann
AU  - Gross J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Brain Res Mol Brain Res
JT  - Brain research. Molecular brain research
JID - 8908640
RN  - 0 (Annexin A5)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (HIF1A protein, human)
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 (Transcription Factors)
RN  - 36015-30-2 (Propidium)
RN  - 9061-61-4 (Nerve Growth Factor)
RN  - EC 1.13.12.- (Luciferases)
SB  - IM
MH  - Animals
MH  - Annexin A5
MH  - Apoptosis/drug effects/physiology
MH  - Asphyxia Neonatorum/*metabolism/physiopathology
MH  - Cell Death/drug effects/*physiology
MH  - Cell Survival/drug effects/physiology
MH  - Central Nervous System/*metabolism/physiopathology
MH  - DNA-Binding Proteins/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - Genes, Reporter/drug effects/physiology
MH  - Genetic Vectors/drug effects/physiology
MH  - Humans
MH  - Hypoxia, Brain/*metabolism/physiopathology
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Infant, Newborn
MH  - Luciferases/genetics
MH  - Necrosis
MH  - Nerve Growth Factor/*metabolism/pharmacology
MH  - Neurons/drug effects/*metabolism
MH  - Nuclear Proteins/*metabolism
MH  - PC12 Cells
MH  - Phenotype
MH  - Propidium
MH  - Rats
MH  - *Transcription Factors
EDAT- 2002/07/16 10:00
MHDA- 2002/11/26 04:00
CRDT- 2002/07/16 10:00
PHST- 2002/07/16 10:00 [pubmed]
PHST- 2002/11/26 04:00 [medline]
PHST- 2002/07/16 10:00 [entrez]
AID - S0169328X02001985 [pii]
AID - 10.1016/s0169-328x(02)00198-5 [doi]
PST - ppublish
SO  - Brain Res Mol Brain Res. 2002 Jul 15;104(1):21-30. doi: 
      10.1016/s0169-328x(02)00198-5.