title: Protection of differentiated neuronal NG108-15 cells from P2X7 receptor-mediated toxicity by taurine.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  The neuroprotective effect by taurine is attributed to the suppression of P2X7R-mediated ER stress and ROS formation.
authors.affiliation: Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Chia-Chia
authors.initials: CC
authors.lastname: Chao
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Medical University Wan Fang Hospital, Taipei, Taiwan.
authors.forename: Paul
authors.initials: P
authors.lastname: Chan
authors.affiliation: Graduate Institute of Neural and Cognitive Sciences, China Medical University, Taichung, Taiwan.
authors.forename: Chang-Shin
authors.initials: CS
authors.lastname: Kuo
authors.affiliation: Department of Physiology, China Medical University, Taichung, Taiwan.
authors.forename: Chi-Li
authors.initials: CL
authors.lastname: Gong
authors.affiliation: Department of Biological Sciences and Technology, China Medical University, Taichung, Taiwan.
authors.forename: Tzu-Hurng
authors.initials: TH
authors.lastname: Cheng
authors.affiliation: Department of Cardiovascular Surgery, Shanghai East Hospital, Tongji University, Shanghai, China.
authors.forename: Zhong-Min
authors.initials: ZM
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Shanghai East Hospital, Tongji University, Shanghai, China.
authors.forename: Pei-Chen
authors.initials: PC
authors.lastname: Shen
authors.affiliation: Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan. Electronic address: cchuang@dragon.nchu.edu.tw.
authors.forename: Chieh-Chen
authors.initials: CC
authors.lastname: Huang
authors.affiliation: Graduate Institute of Neural and Cognitive Sciences, China Medical University, Taichung, Taiwan. Electronic address: ymleung@mail.cmu.edu.tw.
authors.forename: Yuk-Man
authors.initials: YM
authors.lastname: Leung
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000633:toxicity; D000818:Animals; D002118:Calcium / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D058911:Purinergic P2X Receptor Agonists / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism*; D013654:Taurine / Q000494:pharmacology*
chemical_list: D018696:Neuroprotective Agents; D058911:Purinergic P2X Receptor Agonists; D017382:Reactive Oxygen Species; D058486:Receptors, Purinergic P2X7; D013654:Taurine; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; D000255:Adenosine Triphosphate; D002118:Calcium
keywords: Ca(2+) store; ER stress; NG108-15 cells; Neurotoxicity; Taurine