Cannabinoids modulate nitric oxide (NO) levels in cells of the centralnervous system. Here the authors studied the effect of cannabinoid CB1 andCB2 receptor agonists on the release of NO and cell toxicity induced by thehuman immunodeficiency virus-1 Tat protein (HIV-1 Tat) in rat glioma C6cells. The CB1 and CB2 agonist WIN 55,212-2 inhibited the expression ofinducible NO synthase (iNOS) and NO release caused by treatment of C6 cellswith HIV-1 Tat and interferon-g (IFN-g). The effect of WIN 55,212-2 was uniquely due to CB1 receptors, as shown by expts. carried out withselective CB1 and CB2 receptor agonists and antagonists. CB1 receptorstimulation also inhibited HIV-1 Tat + IFN-g-induced and NO-mediated celltoxicity. Moreover, cell treatment with HIV-1 Tat + IFN-g induced asignificant inhibition of CB1, but not CB2, receptor expression. Thiseffect was mimicked by the NO donor GSNO, suggesting that the inhibition ofCB1 expression was due to HIV-1 Tat + IFN-g-induced NO overexpression. HIV-1 Tat + IFN-g treatment also induced a significant inhibition of theuptake of the endocannabinoid anandamide by C6 cells with no effect onanandamide hydrolysis. These findings show that the endocannabinoidsystem, through the modulation of the L-arginine/NO pathway, reduces HIV-1Tat-induced cytotoxicity, and is itself regulated by HIV-1 Tat.
The endocannabinoid system protects rat glioma cells against HIV-1 Tat protein-induced cytotoxicity.
Ligresti A;Ruvo M;
2002
Abstract
Cannabinoids modulate nitric oxide (NO) levels in cells of the centralnervous system. Here the authors studied the effect of cannabinoid CB1 andCB2 receptor agonists on the release of NO and cell toxicity induced by thehuman immunodeficiency virus-1 Tat protein (HIV-1 Tat) in rat glioma C6cells. The CB1 and CB2 agonist WIN 55,212-2 inhibited the expression ofinducible NO synthase (iNOS) and NO release caused by treatment of C6 cellswith HIV-1 Tat and interferon-g (IFN-g). The effect of WIN 55,212-2 was uniquely due to CB1 receptors, as shown by expts. carried out withselective CB1 and CB2 receptor agonists and antagonists. CB1 receptorstimulation also inhibited HIV-1 Tat + IFN-g-induced and NO-mediated celltoxicity. Moreover, cell treatment with HIV-1 Tat + IFN-g induced asignificant inhibition of CB1, but not CB2, receptor expression. Thiseffect was mimicked by the NO donor GSNO, suggesting that the inhibition ofCB1 expression was due to HIV-1 Tat + IFN-g-induced NO overexpression. HIV-1 Tat + IFN-g treatment also induced a significant inhibition of theuptake of the endocannabinoid anandamide by C6 cells with no effect onanandamide hydrolysis. These findings show that the endocannabinoidsystem, through the modulation of the L-arginine/NO pathway, reduces HIV-1Tat-induced cytotoxicity, and is itself regulated by HIV-1 Tat.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
