Protection of differentiated neuronal NG108-15 cells from P2X7 receptor-mediated toxicity by taurine

Background Strong P2X7 receptor (P2X7R) activation causes Ca²⁺ overload and consequent cell death. We previously showed that depletion of Ca²⁺ stores and endoplasmic reticulum (ER) stress in differentiated NG108-15 neuronal cells contributed to P2X7R-mediated cytotoxicity. In this work, we assessed whether taurine (2-aminoethanesulfonic acid) could prevent this P2X7R-mediated cytotoxicity in this neuronal cell line. Methods Cytotoxicity markers were assessed by MTT assay and Western blotting. Cytosolic Ca²⁺ and mitochondrial Ca²⁺ concentrations were measured microfluorimetrically using fura-2 and rhod-2, respectively. Intracellular reactive oxygen species (ROS) production was assayed by the indicator 2′,7′-dichlorodihydrofluorescein diacetate. Results Selective P2X7R agonist BzATP treatment causes neuronal cell death by causing cytosolic Ca ²⁺ overload, depletion of Ca²⁺ stores, endoplasmic reticulum (ER) stress, and caspase-3 activation (cleaved caspase 3). Remarkably, taurine (10 mM) pretreatment could prevent P2X7R-mediated neuronal cell death by blocking BzATP-mediated ER stress as determined by phosphorylated eukaryotic translation initiation factor 2α (peIF2α) and C/EBP-homologous protein (CHOP). However, taurine did not block BzATP-induced Ca²⁺ overload and depletion of ER Ca²⁺ stores. Interestingly, P2X7R activation did not result in mitochondrial Ca²⁺ overload, nor did it affect mitochondrial membrane potential. BzATP-induced generation of intracellular reactive oxygen species (ROS) was prevented by taurine. Conclusions The neuroprotective effect by taurine is attributed to the suppression of P2X7R-mediated ER stress and ROS formation.