Nitric oxide inhibits tumor necrosis factor-alpha-induced apoptosis by reducing the generation of ceramide
| Autor: | Orazio Cantoni, Céline De Nadai, Jacopo Meldolesi, Rico Barsacchi, Emilio Clementi, Piero Sestili, Clara Sciorati, Salvador Moncada, Jean Philippe Lièvremont |
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| Rok vydání: | 2000 |
| Předmět: |
Ceramide
Death receptors Apoptosis S-Nitroso-N-Acetylpenicillamine Ceramides Caspase 8 Nitric Oxide Second Messenger Systems Receptors Tumor Necrosis Factor chemistry.chemical_compound Antigens CD Sphingosine Quinoxalines Humans Nitric Oxide Donors Enzyme Inhibitors Receptor Cyclic GMP Caspase Oxadiazoles Multidisciplinary biology Tumor Necrosis Factor-alpha Penicillamine Proteins U937 Cells Lipid signaling Biological Sciences TNF Receptor-Associated Factor 1 TRADD Caspase 9 Cell biology Kinetics chemistry Receptors Tumor Necrosis Factor Type I Caspases biology.protein Tumor necrosis factor alpha Signal Transduction |
| Popis: | Apoptosis triggered by death receptors proceeds after defined signal-transduction pathways. Whether signaling at the receptor level is regulated by intracellular messengers is still unknown. We have investigated the role of two messengers, ceramide and nitric oxide (NO), on the apoptotic pathway activated in human monocytic U937 cells by tumor necrosis factor-alpha (TNF-alpha) working at its p55 receptor. Two transduction events, the receptor recruitment of the adapter protein, TRADD, and the activation of the initiator caspase, caspase 8, were investigated. When administered alone, neither of the messengers had any effect on these events. In combination with TNF-alpha, however, ceramide potentiated, whereas NO inhibited, TNF-alpha-induced TRADD recruitment and caspase 8 activity. The effect of NO, which was cGMP-dependent, was due to inhibition of the TNF-alpha-induced generation of ceramide. Our results identify a mechanism of regulation of a signal-transduction pathway activated by death receptors. |
| Databáze: | OpenAIRE |
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