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Ceramide Induces Apoptosis in Cultured Mesencephalic Neurons
Author(s) -
Brugg Bernard,
Michel Patrick P.,
Agid Yves,
Ruberg Merle
Publication year - 1996
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 - 10.1046/j.1471-4159.1996.66020733.x
Subject(s) - ceramide , apoptosis , cycloheximide , programmed cell death , biology , microbiology and biotechnology , dna fragmentation , sphingomyelin , sphingosine , lipid signaling , biochemistry , protein biosynthesis , membrane , receptor
The death of dopaminergic and other neurons in primary cultures of the mesencephalon could be induced by treatment with ceramide, as in lymphocytes where it mediates activation by the cytokines tumor necrosis factor‐α and interleukin‐1β of a novel sphingomyelin‐dependent signaling pathway leading to apoptosis. The morphological hallmarks of this form of cell death—bleb formation, cell body shrinkage, nuclear chromatin condensation, and fragmentation—were observed in degenerating neurons. Internucleosomal DNA degradation could also be evidenced by gel electrophoresis. The C 2 and C 6 analogues as well as native ceramide, administered in a dodecane suspension, had a similar effect, whereas the closely related C 2 ‐dihydroceramide, which lacks the 4–5 trans double bond in the sphingosine chain, failed to induce apoptosis. Neuronal death could be delayed by serum factors, dibutyryl cyclic AMP, and the protein synthesis inhibitor cycloheximide.

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