Neural progenitor cell death is induced by extracellular ATP via ligation of P2X7 receptor
Article first published online: 24 FEB 2009
© 2009 The Authors. Journal Compilation © 2009 International Society for Neurochemistry
Journal of Neurochemistry
Volume 109, Issue 3, pages 846–857, May 2009
How to Cite
Delarasse, C., Gonnord, P., Galante, M., Auger, R., Daniel, H., Motta, I. and Kanellopoulos, J. M. (2009), Neural progenitor cell death is induced by extracellular ATP via ligation of P2X7 receptor. Journal of Neurochemistry, 109: 846–857. doi: 10.1111/j.1471-4159.2009.06008.x
- Issue published online: 7 APR 2009
- Article first published online: 24 FEB 2009
- Received August 25 2008; revised manuscript received February 3, 2009; accepted February 18, 2009.
- cell death;
- neural progenitor cell;
- P2X7 receptor
J. Neurochem. (2009) 109, 846–857.
Neural progenitor cells (NPCs) are capable of self-renewal and differentiation into neurons, astrocytes and oligodendrocytes, and have been used to treat several animal models of CNS disorders. In the present study, we show that the P2X7 purinergic receptor (P2X7R) is present on NPCs. In NPCs, P2X7R activation by the agonists extracellular ATP or benzoyl ATP triggers opening of a non-selective cationic channel. Prolonged activation of P2X7R with these nucleotides leads to caspase independent death of NPCs. P2X7R ligation induces NPC lysis/necrosis demonstrated by cell membrane disruption accompanied with loss of mitochondrial membrane potential. In most cells that express P2X7R, sustained stimulation with ATP leads to the formation of a non-selective pore allowing the entry of solutes up to 900 Da, which are reportedly involved in P2X7R-mediated cell lysis. Surprisingly, activation of P2X7R in NPCs causes cell death in the absence of pore formation. Our data support the notion that high levels of extracellular ATP in inflammatory CNS lesions may delay the successful graft of NPCs used to replace cells and repair CNS damage.