Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2006-11-1
pubmed:abstractText
Oxygen and glucose deprivation are direct consequences of tissue ischaemia. We explored the interaction of hypoxia and hypoglycaemia on cell survival and gene expression in the absence of glutamatergic signalling using human SH-SY5Y neuroblastoma cells as a model. In agreement with previous investigations in non-neural cells, prolonged hypoxia (0.5% O(2)) failed to induce significant cell death in this system. In contrast, exposure to hypoglycaemia induced significant necrotic cell death (> 80% after 72 h). Interestingly, hypoglycaemia-induced cell death was completely abrogated by simultaneous exposure to hypoxia, suggesting strong cytoprotective effects of hypoxia. Subsequent microarray analysis of the underlying transcriptional responses revealed that the transcription factor CEBP homology protein (CHOP) was strongly induced by hypoglycaemia, and suppressed by simultaneous hypoxia. RNA interference against CHOP significantly protected cells from glucose deprivation-induced cell death. Hypoxia-induced vascular endothelial growth factor (VEGF) activation also protected cells against hypoglycaemia-induced cell death, but VEGF failed to modify hypoglycaemia-induced CHOP induction. Our data suggest that hypoglycaemia-induced necrotic cell death of neuroblastoma cells is an active process mediated via the induction of the transcription factor CHOP, and that hypoxia counteracts this cell death via at least two distinct mechanisms: repression of CHOP and induction of VEGF.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
99
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
952-64
pubmed:meshHeading
pubmed-meshheading:16942595-Anoxia, pubmed-meshheading:16942595-Apoptosis, pubmed-meshheading:16942595-Blotting, Western, pubmed-meshheading:16942595-Brain Neoplasms, pubmed-meshheading:16942595-CCAAT-Enhancer-Binding Proteins, pubmed-meshheading:16942595-Caspase 3, pubmed-meshheading:16942595-Cell Death, pubmed-meshheading:16942595-Cell Line, Tumor, pubmed-meshheading:16942595-Fluorescent Dyes, pubmed-meshheading:16942595-Glucose, pubmed-meshheading:16942595-Humans, pubmed-meshheading:16942595-Hypoglycemia, pubmed-meshheading:16942595-Necrosis, pubmed-meshheading:16942595-Neuroblastoma, pubmed-meshheading:16942595-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:16942595-Signal Transduction, pubmed-meshheading:16942595-Transfection, pubmed-meshheading:16942595-Vascular Endothelial Growth Factor A
pubmed:year
2006
pubmed:articleTitle
Induction of transcription factor CEBP homology protein mediates hypoglycaemia-induced necrotic cell death in human neuroblastoma cells.
pubmed:affiliation
Experimental Neurosurgery, Center for Neurology and Neurosurgery, Johann Wolfgang Goethe University Clinics, Frankfurt, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't