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Ceramide sensitizes astrocytes to oxidative
stress: protective role of cannabinoids
Carracedo A, Geelen MJ, Diez M, Hanada K, Guzman M, Velasco G
Department of Biochemistry and Molecular Biology I, School of
Biology, Complutense University, 28040 Madrid, Spain.
Cannabinoids induce apoptosis on glioma cells via stimulation of ceramide
synthesis de novo, whereas they do not affect viability of primary
astrocytes.
In the present study, we show that incubation with Delta9-tetrahydrocannabinol
did not induce accumulation of ceramide on astrocytes, although incubation of
these cells in a serum-free medium (with or without cannabinoids) led to
stimulation of ceramide synthesis de novo and sensitization to oxidative
stress.
Thus treatment with H2O2 induced apoptosis of 5-day-serum-deprived astrocytes
and this effect was abrogated by pharmacological blockade of ceramide synthesis
de novo.
The sensitizing effect of ceramide accumulation may depend on p38
mitogen-activated protein kinase activation rather than on other ceramide
targets.
Finally, a protective role of cannabinoids on astrocytes is shown as a long-term
incubation with cannabinoids prevented H2O2-induced loss of viability in a CB1
receptor-dependent manner.
In summary, our results show that whereas challenge of glioma cells with
cannabinoids induces accumulation of de novo -synthesized ceramide and
apoptosis, long-term treatment of astrocytes with these compounds does not
stimulate this pathway and also abrogates the sensitizing effects of ceramide
accumulation.
PMID: 14979873 [PubMed - in process]
Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14979873
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