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. © 2014 institute of pharmacology,polish academy of sciences.