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J. Biol. Chem., Vol. 277, Issue 39, 36527-36533, September 27, 2002
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From the Cannabinoids, the active components of marijuana
and their endogenous counterparts, exert many of their actions on the
central nervous system by binding to the CB1
cannabinoid receptor. Different studies have shown that cannabinoids
can protect neural cells from different insults. However, those studies
have been performed in neurons, whereas no attention has been focused
on glial cells. Here we used the pro-apoptotic lipid ceramide to
induce apoptosis in astrocytes, and we studied the protective effect
exerted by cannabinoids. Results show the following: (i) cannabinoids
rescue primary astrocytes from C2-ceramide-induced
apoptosis in a dose- and time-dependent manner; (ii)
triggering of this anti-apoptotic signal depends on the
phosphatidylinositol 3-kinase/protein kinase B pathway; (iii) ERK and
its downstream target p90 ribosomal S6 kinase might be also involved in
the protective effect of cannabinoids; and (iv) cannabinoids protect
astrocytes from the cytotoxic effects of focal C2-ceramide
administration in vivo. In summary, results show that
cannabinoids protect astrocytes from ceramide-induced apoptosis via
stimulation of the phosphatidylinositol 3-kinase/protein kinase B
pathway. These findings constitute the first evidence for an
"astroprotective" role of cannabinoids.
Cannabinoids Protect Astrocytes from Ceramide-induced Apoptosis
through the Phosphatidylinositol 3-Kinase/Protein Kinase B Pathway*
,, and¶
Department of Biochemistry and Molecular
Biology I, School of Biology, Complutense University, 28040 Madrid and
§ Neurodegeneration Group, Cajal Institute, CSIC,
28002 Madrid, Spain
*
This work was supported by Ministerio de Ciencia y
Tecnologia (MCYT) Grants PM 98/0079, CAM 08.1/0079/2000, and
Fundación Ramón Areces.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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