Induction of transcription factor CEBP homology protein mediates hypoglycaemia-induced necrotic cell death in human neuroblastoma cells.
Donat Kögel,Birte Svensson,Ekaterini Copanaki,Sergio Anguissola,Caroline Bonner,Nadia Thurow,Daniel Gudorf,Holger Hetschko,Thorsten Müller,Marion Peters,Hans-Georg König,Hans-Georg König,Jochen H. M. Prehn +12 more
TLDR
The 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.Abstract:
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.read more
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The Pan-Bcl-2 Inhibitor (−)-Gossypol Triggers Autophagic Cell Death in Malignant Glioma
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Regulation of Tumor Progression by Programmed Necrosis.
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PPARgamma stimulation promotes mitochondrial biogenesis and prevents glucose deprivation-induced neuronal cell loss.
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TL;DR: The data indicate that a prolonged PPARgamma stimulation, by repeated administration of nanomolar pioglitazone or rosiglitaz one concentrations, decreases GD-induced loss of differentiated SH-SY5Y cells, and suggest that mitochondrial biogenesis may contribute to these effects.
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NMDA receptor-mediated excitotoxic neuronal apoptosis in vitro and in vivo occurs in an ER stress and PUMA independent manner.
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TL;DR: In this article, the antiperitoneal dissemination potential of Honokiol in an orthotopic mouse model and assessed associations with tumor growth factor-β1 (TGFβ1) and cells stimulated by a carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG).
References
More filters
Journal ArticleDOI
Cluster analysis and display of genome-wide expression patterns
TL;DR: A system of cluster analysis for genome-wide expression data from DNA microarray hybridization is described that uses standard statistical algorithms to arrange genes according to similarity in pattern of gene expression, finding in the budding yeast Saccharomyces cerevisiae that clustering gene expression data groups together efficiently genes of known similar function.
Journal ArticleDOI
The biology of VEGF and its receptors.
TL;DR: Vascular endothelial growth factor (VEGF) is a key regulator of physiological angiogenesis during embryogenesis, skeletal growth and reproductive functions and is implicated in pathologicalAngiogenesis associated with tumors, intraocular neovascular disorders and other conditions.
Journal ArticleDOI
Angiogenesis in cancer and other diseases
Peter Carmeliet,Rakesh K. Jain +1 more
TL;DR: Pathological angiogenesis is a hallmark of cancer and various ischaemic and inflammatory diseases and integrated understanding is leading to the development of a number of exciting and bold approaches to treat cancer and other diseases, but owing to several unanswered questions, caution is needed.
Journal ArticleDOI
Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium.
TL;DR: The multiple anginal episodes that often precede myocardial infarction in man may delay cell death after coronary occlusion, and thereby allow for greater salvage of myocardium through reperfusion therapy, which is proposed to protect the heart from a subsequent sustained ischemic insult.
Journal ArticleDOI
LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing
Yukiko Kabeya,Noboru Mizushima,Noboru Mizushima,Takashi Ueno,Akitsugu Yamamoto,Takayoshi Kirisako,Takayoshi Kirisako,Takeshi Noda,Takeshi Noda,Eiki Kominami,Yoshinori Ohsumi,Yoshinori Ohsumi,Tamotsu Yoshimori,Tamotsu Yoshimori +13 more
TL;DR: It is demonstrated that the rat microtubule‐associated protein 1 light chain 3 (LC3), a homologue of Apg8p essential for autophagy in yeast, is associated to the autophagosome membranes after processing.