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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1995-9-18
pubmed:abstractText
We show that excitotoxic cell death, which is associated with pathological neurodegenerative processes, can display morphological and biochemical features characteristic of apoptosis, a mode of cell death typical of physiological neuronal elimination during development. Cortical neurons cultured in the absence of serum, stimulated with NMDA, glutamate, or quisqualate after 3-5 days in vitro, showed significant degeneration. This death was blocked by 1 microM MK-801, indicating that it was mediated by the activation of NMDA receptors. Dying cells displayed an apoptotic morphology, characterized by cytoplasm and chromatin condensation. No internucleosomal DNA degradation was observed, confirming that morphological changes of apoptosis can be dissociated from DNA laddering. Inhibitors of protein or RNA synthesis abolished cell death, and the protective effect of cycloheximide was similar when the drug was applied 2 h before or 8 h after glutamate. These experiments suggest the participation of active gene transcription in the mechanism of death. We thus analyzed the modulation of transcription factors in dying cells using electrophoretic mobility shift assays. The level of factors binding to the 12-O-tetradecanoylphorbol 13-acetate-responsive element (TRE) displayed a late and sustained increase preceding neuronal death, which was not found for factors complexing the Sp1 P, Oct, and USF binding sites. These results raise the possibility that apoptosis is one of the mechanisms of death in the pathologies linked to excitotoxicity and that activation of TRE-binding factors could play a role in these processes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
65
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1027-34
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Induction of neuronal apoptosis by excitotoxins associated with long-lasting increase of 12-O-tetradecanoylphorbol 13-acetate-responsive element-binding activity.
pubmed:affiliation
Laboratoire mixte Rhône-Poulenc Rorer/CNRS, Génétique, Moléculaire de la Neurotransmission et des Processus Neurodégénératifs, CNRS, Gif sur Yvette, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't