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

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)576-584
Number of pages9
JournalPharmacological Reports
Volume66
Issue number4
DOIs
Publication statusPublished - 2014

Keywords

  • ER stress
  • Neurotoxicity
  • NG108-15 cells
  • Taurine

ASJC Scopus subject areas

  • Pharmacology
  • Medicine(all)

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