v v W -Tetrahydrocannabinol (THC), the major active component of marijuana, induced apoptosis in C6.9 glioma cells, as determined by DNA fragmentation and loss of plasma membrane asymmetry. THC stimulated sphingomyelin hydrolysis in C6.9 glioma cells. THC and N-acetylsphingosine, a cellpermeable ceramide analog, induced apoptosis in several transformed neural cells but not in primary astrocytes or neurons. Although glioma C6.9 cells expressed the CB1 cannabinoid receptor, neither THC-induced apoptosis nor THC-induced sphingomyelin breakdown were prevented by SR141716, a specific antagonist of that receptor. Results thus show that THC-induced apoptosis in glioma C6.9 cells may rely on a CB1 receptor-independent stimulation of sphingomyelin breakdown.z 1998 Federation of European Biochemical Societies.

Astrocytes play a pivotal role in CNS detoxification pathways, where glutathione (GSH) is involved in the elimination of oxygen and nitrogen reactive species such as nitric oxide. We have previously demonstrated that the specific activity of ␥-glutamyl transpeptidase (␥-GT), an enzyme of central significance in GSH metabolism, is regulated in vivo in astrocytes by 1,25-dihydroxyvitamin D 3 (1,25-D 3 ). The aim of the present work was to investigate, in primary cultures of newborn rat astrocytes, the effects of this hormone on ␥-GT synthesis and on GSH and nitrite levels after lipopolysaccharide (LPS) treatment. This study demonstrates that both ␥-GT gene expression and specific activity, induced by LPS, are potentiated by 1,25-D 3 . In contrast, 1,25-D 3 does not regulate the expression of other enzymes involved in astrocyte detoxification processes, such as superoxide dismutase or GSH peroxidase. In parallel, 1,25-D 3 enhanced intracellular GSH pools and significantly reduced nitrite production induced by LPS. Taken together, these results suggest that ␥-GT, GSH, and 1,25-D 3 play a fundamental role in astrocyte detoxification pathways.

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