Linked Life Data

10579204

Source:http://linkedlifedata.com/resource/pubmed/id/10579204

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1999-12-21
pubmed:abstractText
In this study, we report that mobilization of internal Ca2+ by sphingosine-1-phosphate, a metabolite of ceramide, induces apoptosis in cultured hippocampal neurons. This sphingosine-1-phosphate-induced apoptosis is dependent upon the activation of protein phosphatases, possibly calcineurin and phosphatase 2A (or a related phosphatase). In addition, pretreatment of neurons with double-stranded oligonucleotides containing the metallothionein phorbol-12-myristate-13-acetate response element sequence as transcription factor decoys suppressed apoptosis. In contrast, double-stranded oligonucleotides containing either the c-jun or SV40 phorbol-12-myristate-13-acetate response element sequences were ineffective. Electrophoretic mobility shift assays and supershift assays revealed that c-Fos-containing activator protein- complexes preferentially bound the metallothionein phorbol-12-myristate-13-acetate response element sequence-containing oligonucleotides. Furthermore, antisense oligonucleotides to c-fos and c-jun were also protective. The apoptotic death of hippocampal neurons has been hypothesized to contribute to the cognitive impairments observed following insults to the brain. While increases in intracellular calcium are thought to be key mediators of neuronal apoptosis, the biochemical cascade(s) activated as a result of increased Ca2+ which mediates apoptosis of hippocampal neurons is (are) not well understood. The findings presented in this study suggest that mobilization of internal calcium via prolonged exposure of sphingosine-1-phosphate induces apoptosis of hippocampal neurons in culture. Sustained increases in intracellular calcium activate a phosphatase cascade that includes calcineurin and a phosphatase 2A-like phosphatase, and leads to the expression of genes containing metallothionein phorbol-12-myristate-13-acetate response element (TGAGTCA)-type enhancer sequences. The expression of genes containing TGAGTCA-type enhancer sequences appears to be essential for sphingosine-1-phosphate-induced apoptosis of hippocampal neurons.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0306-4522
pubmed:author
pubmed:issnType
Print
pubmed:volume
94
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
405-15
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:10579204-Animals, pubmed-meshheading:10579204-Apoptosis, pubmed-meshheading:10579204-Base Sequence, pubmed-meshheading:10579204-Cells, Cultured, pubmed-meshheading:10579204-Fetus, pubmed-meshheading:10579204-Genes, fos, pubmed-meshheading:10579204-Genes, jun, pubmed-meshheading:10579204-Hippocampus, pubmed-meshheading:10579204-Kinetics, pubmed-meshheading:10579204-Lysophospholipids, pubmed-meshheading:10579204-Neurons, pubmed-meshheading:10579204-Oligodeoxyribonucleotides, pubmed-meshheading:10579204-Oligodeoxyribonucleotides, Antisense, pubmed-meshheading:10579204-Phosphoprotein Phosphatases, pubmed-meshheading:10579204-Protein Phosphatase 2, pubmed-meshheading:10579204-Rats, pubmed-meshheading:10579204-Regulatory Sequences, Nucleic Acid, pubmed-meshheading:10579204-Sphingosine, pubmed-meshheading:10579204-Tetradecanoylphorbol Acetate, pubmed-meshheading:10579204-Transcription Factor AP-1
pubmed:year
1999
pubmed:articleTitle
Sphingosine-1-phosphate induces apoptosis of cultured hippocampal neurons that requires protein phosphatases and activator protein-1 complexes.
pubmed:affiliation
Department of Neurobiology and Anatomy, W. M. Keck Center for the Neurobiology of Learning and Memory, The University of Texas Medical School, Houston 77225, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't