Premium
Induction of transcription factor CEBP homology protein mediates hypoglycaemia‐induced necrotic cell death in human neuroblastoma cells
Author(s) -
Kögel Donat,
Svensson Birte,
Copanaki Ekaterini,
Anguissola Sergio,
Bonner Caroline,
Thurow Nadia,
Gudorf Daniel,
Hetschko Holger,
Müller Thorsten,
Peters Marion,
König HansGeorg,
Prehn Jochen H. M.
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04135.x
Subject(s) - programmed cell death , biology , chop , apoptosis , transcription factor , hypoxia (environmental) , cancer research , cell , endocrinology , microbiology and biotechnology , medicine , chemistry , biochemistry , gene , organic chemistry , oxygen
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.