ATP Signaling and Oligodendrocyte Toxicity
Posted: Sat Sep 01, 2007 6:28 am
ATP is a vital molecule within cells for the transfer of energy, but now it looks set to join glutamate for its role in excitotoxicity
ATP Signaling and Oligodendrocyte Toxicity
Carlos Matute, Iratxe Torre, Fernando Pérez-Cerdá, Alberto Pérez-Samartín, Elena Alberdi, Estibaliz Etxebarria, Amaia M. Arranz, Rivka Ravid, Alfredo Rodríguez-Antigüedad, María Victoria Sánchez-Gómez, and María Domercq
Excitotoxicity used to be synonymous with too much glutamate, but when it comes to oligodendrocytes, it seems that excitotoxicity also can mean too much ATP. This week, Matute et al. provide evidence that ATP can cause excitotoxic damage by activating P2X7 purinergic receptors and increasing intracellular calcium. In cultured rat oligodendrocytes, ATP triggered nondesensitizing P2X7 currents that proved toxic under conditions of sustained ATP exposure. Toxicity was prevented when calcium was removed from the media, or in the presence of P2X receptor antagonists. In whole optic nerves, both isolated and in vivo, ATP perfusion increased oligodendrocyte death. P2X agonists produced oligodendrocyte death, demyelination, and axonal damage reminiscent of multiple sclerosis lesions. P2X7 antagonists reduced motor deficits and demyelination in mice, in which experimental autoimmune encephalomyelitis (EAE) had been induced by myelin oligodendrocyte glycoprotein (MOG) immunization. ATP-induced oligodendrocyte death could contribute to the tissue damage associated with EAE and multiple sclerosis.
ATP Signaling and Oligodendrocyte Toxicity
Carlos Matute, Iratxe Torre, Fernando Pérez-Cerdá, Alberto Pérez-Samartín, Elena Alberdi, Estibaliz Etxebarria, Amaia M. Arranz, Rivka Ravid, Alfredo Rodríguez-Antigüedad, María Victoria Sánchez-Gómez, and María Domercq
Excitotoxicity used to be synonymous with too much glutamate, but when it comes to oligodendrocytes, it seems that excitotoxicity also can mean too much ATP. This week, Matute et al. provide evidence that ATP can cause excitotoxic damage by activating P2X7 purinergic receptors and increasing intracellular calcium. In cultured rat oligodendrocytes, ATP triggered nondesensitizing P2X7 currents that proved toxic under conditions of sustained ATP exposure. Toxicity was prevented when calcium was removed from the media, or in the presence of P2X receptor antagonists. In whole optic nerves, both isolated and in vivo, ATP perfusion increased oligodendrocyte death. P2X agonists produced oligodendrocyte death, demyelination, and axonal damage reminiscent of multiple sclerosis lesions. P2X7 antagonists reduced motor deficits and demyelination in mice, in which experimental autoimmune encephalomyelitis (EAE) had been induced by myelin oligodendrocyte glycoprotein (MOG) immunization. ATP-induced oligodendrocyte death could contribute to the tissue damage associated with EAE and multiple sclerosis.