Neuroscience 2000 Abstract
| Presentation Number: | 814.2 |
|---|---|
| Abstract Title: | Mechanism of cannabinoid-induced ceramide accumulation and apoptosis in glial cells. |
| Authors: |
Galve-Roperh, I.*1
; Sánchez, C.1
; Rueda , D.1
; Gomez del Pulgar, M. T.1
; Guzmán, M.1
1Dept Biochem & Molec Biol I, Complutense Univ, Madrid 28040, Spain |
| Primary Theme and Topics |
D. Neurotransmitters, Modulators, Transporters, and Receptors - 54. Cannabinoids |
| Secondary Theme and Topics | D. Neurotransmitters, Modulators, Transporters, and Receptors<br />- 59. Second messengers and phosphorylation |
| Session: |
814. Cannabinoids: receptor actions Poster |
| Presentation Time: | Thursday, November 9, 2000 9:00 AM-10:00 AM |
| Location: | Hall G-J |
| Keywords: | APOPTOSIS, GLIOMA, THC, PHOSPHOLIPID |
Cannabinoids, the active components of marijuana and their endogenous counterparts, exert their effects on the central nervous system through the CB1 receptor. This G-protein-coupled receptor has been shown to be functionally coupled to inhibition of adenylyl cyclase, activation of extracellular signal-regulated kinase and modulation of ion channels. This study was undertaken to test whether the CB1 receptor is coupled to ceramide generation, which may be involved in the control of cell fate. (a) Short-term incubation with cannabinoids induced sphingomyelin breakdown and ceramide accumulation in primary astrocytes and C6 glioma cells, but not in primary neurons. Cannabinoid-induced sphingomyelin hydrolysis was dependent on CB1 receptor activation but independent of Gi/o proteins. A role for the adaptor protein FAN is supported by coimmunoprecipitation experiments and by the use of cells overexpressing wild-type or dominant-negative forms of FAN. (b) Long-term incubation of C6 glioma cells with cannabinoids induced sustained ceramide accumulation and apoptosis. These effects were prevented by L-cycloserine, an inhibitor of ceramide synthesis de novo, but not by various sphingomyelinase inhibitors. A subclone of C6 glioma cells in which sustained ceramide accumulation did not occur upon cannabinoid challenge was also reluctant to cannabinoid-induced apoptosis. Results show therefore that cannabinoids evoke a short- and a long-term peak of ceramide, and that only the latter peak is involved in the induction of apoptosis.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2000 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2000. Online.
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