Atp-induced Apoptosis of Thymocytes is Mediated by Activation of P2 X 7 Receptor and Involves De Novo Ceramide Synthesis and Mitochondria.
From: Biomembranes et Messagers Cellulaires, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8619, Université Paris XI-Orsay, France.
Biochimica et biophysica acta
- Publish Date: Jan 2006
- ISSN: 0006-3002
- Volume: 1761
- Issue: 1
- Pages: 73-82
- Medium: Print
- Language: English
- Citation (JAMA): Lépine S, Le Stunff H, Lakatos B, et al. Atp-induced Apoptosis of Thymocytes is Mediated by Activation of P2 X 7 Receptor and Involves De Novo Ceramide Synthesis and Mitochondria.. Biochim. Biophys. Acta Jan 2006;1761:73-82
Abstract
Thymocytes were reported to undergo apoptosis in the presence of extracellular ATP through the activation of the purinergic receptors P2 X 1R, P2 X 7R or both. We investigated the identity of the P2 X R and the signaling pathways involved in ATP-mediated apoptosis. Apoptosis elicited by ATP was prevented by inhibition of P2 X 7R, or in thymocytes bearing a mutated P2 X 7R, and reproduced with a P2 X 7R agonist, but not with a P2 X 1R agonist. Stimulation of thymocytes with either ATP or a P2 X 7R agonist was found to stimulate a late de novo ceramide synthesis and mitochondrial alterations. Inhibition of either processes attenuated apoptosis. Interestingly, stimulation with either ATP or a P2 X 1R agonist induced an early ceramide accumulation and a weak caspases-3/7 activation that did not lead to apoptosis. In conclusion, de novo ceramide generation and mitochondrial alterations, both resulting from P2 X 7R activation, were implicated in ATP-induced thymocyte apoptosis.
Mesh Headings (Keywords): Adenosine Triphosphate, Animals, Apoptosis, Cells, Cultured, Ceramides, Kinetics, Mice, Mice, Inbred BALB C, Mitochondria, Receptors, Purinergic P2, Sphingosine, T-Lymphocytes
Check for Full Text / PubMed Unique Identifier (PMID): 16325464
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