Trail interacts redundantly with nitric oxide in rat astrocytes: potential contribution to neurodegenerative processes.
The proapoptotic cytokine TRAIL has been shown to enhance amyloid-beta-dependent neurotoxicity. Here are reported interactions between TRAIL and nitric oxide (NO) in cultured rat astrocytes in vitro. Rat astrocytes expressed all TRAIL receptor mRNAs and proteins. However, TRAIL failed in inducing apoptosis of astrocytes, whereas these cells released substantial amounts of nitrites. A TRAIL-neutralizing antibody was able to prevent LPS-induced iNOS expression in astrocytes. Interestingly, TRAIL induced its own expression in astrocytes. These data suggest that redundancy between TRAIL and NO in astrocytes could be fueling neuronal damage/death processes, potentially uncovering novel molecular targets for the treatment of neurodegenerative disorders.
Cantarella
Giuseppina
G
Department of Experimental and Clinical Pharmacology, University of Catania, Viale Andrea Doria, 6, I-95125 Catania, Italy.
Lempereur
Laurence
L
D'Alcamo
Maria Antonia
MA
Risuglia
Nunziata
N
Cardile
Vera
V
Pennisi
Giuseppa
G
Scoto
Giovanna Maria
GM
Bernardini
Renato
R
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D002478:Cells, Cultured; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D009410:Nerve Degeneration; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*
D000906:Antibodies; D009573:Nitrites; D012333:RNA, Messenger; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D020928:Mitogen-Activated Protein Kinases