Pharmacological reports : PR 2014-08-01

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

Chia-Chia Chao, Paul Chan, Chang-Shin Kuo, Chi-Li Gong, Tzu-Hurng Cheng, Zhong-Min Liu, Pei-Chen Shen, Chieh-Chen Huang, Yuk-Man Leung

文献索引：Pharmacol. Rep. 66(4) , 576-84, (2014)

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摘要

Strong P2X7 receptor (P2X7R) activation causes Ca(2+) overload and consequent cell death. We previously showed that depletion of Ca(2+) 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.Cytotoxicity markers were assessed by MTT assay and Western blotting. Cytosolic Ca(2+) and mitochondrial Ca(2+) 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.Selective P2X7R agonist BzATP treatment causes neuronal cell death by causing cytosolic Ca(2+) overload, depletion of Ca(2+) stores, endoplasmic reticulum (ER) stress, and caspase-3 activation (cleaved caspase 3). Remarkably, taurine (10mM) 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 Ca(2+) overload and depletion of ER Ca(2+) stores. Interestingly, P2X7R activation did not result in mitochondrial Ca(2+) overload, nor did it affect mitochondrial membrane potential. BzATP-induced generation of intracellular reactive oxygen species (ROS) was prevented by taurine.The neuroprotective effect by taurine is attributed to the suppression of P2X7R-mediated ER stress and ROS formation.Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.