The endocannabinoid system protects rat glioma cells against HIV-1 Tat protein-induced cytotoxicity: Mechanism and regulation(471 views) Esposito G, Ligresti A, Izzo AA, Bisogno T, Ruvo M, Di Rosa M, Di Marzo V, Iuvone T
Dept. of Experimental Pharmacology, University of Naples Federico II, Via D. Montesano 49, 80131 Naples, Italy
Endocannabinoid Research Group, Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, 80078 Pozzuoli, Naples, Italy
Ist. di Biostrutture e Bioimmagini, Consiglio Nazionale delle Ricerche, Via Mezzocannone 6, 80134 Naples, Italy
Comprensorio Olivetti, Ed. 70, Via Campi Flegrei 34, 80078 Pozzuoli, Naples, Italy
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The endocannabinoid system protects rat glioma cells against HIV-1 Tat protein-induced cytotoxicity: Mechanism and regulation
Cannabinoids modulate nitric oxide (NO) levels in cells of the central nervous system. Here we studied the effect of cannabinoid CB1 and CB2 receptor agonists on the release of NO and cell toxicity induced by the human immuno-deficiency virus-1 Tat protein (HIV-1 Tat) in rat glioma C6 cells. The CB1 and CB2 agonist WIN 55,212-2 inhibited the expression of inducible NO synthase (iNOS) and NO release caused by treatment of C6 cells with HIV-1 Tat and interferon-γ (IFN-γ). The effect of WIN 55,212-2 was uniquely due to CB1 receptors, as shown by experiments carried out with selective CB1 and CB2 receptor agonists and antagonists. CB1 receptor stimulation also inhibited HIV-1 Tat + IFN-γ-induced and NO-mediated cell toxicity. Moreover, cell treatment with HIV-1 Tat + IFN-γ induced a significant inhibition of CB1, but not CB2, receptor expression. This effect was mimicked by the NO donor GSNO, suggesting that the inhibition of CB1 expression was due to HIV-1 Tat + IFN-γ-induced NO overexpression. HIV-1 Tat + IFN-γ treatment also induced a significant inhibition of the uptake of the endocannabinoid anandamide by C6 cells with no effect on anandamide hydrolysis. These findings show that the endocannabinoid system, through the modulation of the L-arginine/NO pathway, reduces HIV-1 Tat-induced cytotoxicity, and is itself regulated by HIV-1 Tat.
The endocannabinoid system protects rat glioma cells against HIV-1 Tat protein-induced cytotoxicity: Mechanism and regulation
No results.
The endocannabinoid system protects rat glioma cells against HIV-1 Tat protein-induced cytotoxicity: Mechanism and regulation
Testino G, Leone S, Fagoonee S, Del Bas JM, Rodriguez B, Puiggros F, Marine S, Rodriguez MA, Morina D, Armengol L, Caimari A, Arola L, Cimini FA, Barchetta I, Carotti S, Bertoccini L, Baroni MG, Vespasiani-gentilucci U, Cavallo MG, Morini S, Nelson JE, Roth CL, Wilson LA, Yates KP, Aouizerat B, Morgan-stevenson V, Whalen E, Hoofnagle A, Mason M, Gersuk V, Yeh MM, Kowdley KV, Lee SM, Jun DW, Cho YK, Jang KS, Kucukazman M, Ata N, Dal K, Yeniova AO, Kefeli A, Basyigit S, Aktas B, Akin KO, Agladioglu K, Ure OS, Topal F, Nazligul Y, Beyan E, Ertugrul DT, Catena C, Cosma C, Camozzi V, Plebani M, Ermani M, Sechi LA, Fallo F, Goto Y, Ray MB, Mendenhall CL, French SW, Gartside PS Serum vitamin A deficiency and increased intrahepatic expression of cytokeratin antigen in alcoholic liver disease(600 views) Hepatology (ISSN: 1827-1669electronic, 0026-4806linking), 1988 Sep; 83120693611123109(5): 1019-1026. Impact Factor:0.913 ViewExport to BibTeXExport to EndNote