Identification of genes involved in ceramide-dependent neuronal apoptosis using cDNA arrays.
BACKGROUND
Ceramide is important in many cell responses, such as proliferation, differentiation, growth arrest and apoptosis. Elevated ceramide levels have been shown to induce apoptosis in primary neuronal cultures and neuronally differentiated PC 12 cells.


RESULTS
To investigate gene expression during ceramide-dependent apoptosis, we carried out a global study of gene expression in neuronally differentiated PC 12 cells treated with C2-ceramide using an array of 9,120 cDNA clones. Although the criteria adopted for differential hybridization were stringent, modulation of expression of 239 genes was identified during the effector phase of C2-ceramide-induced cell death. We have made an attempt at classifying these genes on the basis of their putative functions, first with respect to known effects of ceramide or ceramide-mediated transduction systems, and then with respect to regulation of cell growth and apoptosis.


CONCLUSIONS
Our cell-culture model has enabled us to establish a profile of gene expression during the effector phase of ceramide-mediated cell death. Of the 239 genes that met the criteria for differential hybridization, 10 correspond to genes previously involved in C2-ceramide or TNF-alpha signaling pathways and 20 in neuronal disorders, oncogenesis or more broadly in the regulation of proliferation. The remaining 209 genes, with or without known functions, constitute a pool of genes potentially implicated in the regulation of neuronal cell death.
Decraene
Charles
C
Genexpress, CNRS FRE 2376, BP8, 94801 Villejuif, France.
Brugg
Bernard
B
Ruberg
Merle
M
Eveno
Eric
E
Matingou
Christiane
C
Tahi
Fariza
F
Mariani
Jean
J
Auffray
Charles
C
Pietu
Geneviève
G
D000818:Animals; D017209:Apoptosis / Q000235:genetics* / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D020869:Gene Expression Profiling / Q000379:methods; D005796:Genes; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D009693:Nucleic Acid Hybridization / Q000379:methods; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D016716:PC12 Cells; D051381:Rats; D015398:Signal Transduction / Q000235:genetics; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000502:physiology*
C064769:N-acetylsphingosine; D013110:Sphingosine