Home » Key Scientific Articles » Protection of differentiated neuronal NG108-15 cells from P2X7 receptor-mediated toxicity by taurine.

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

Chao CC1, Chan P2, Kuo CS3, Gong CL4, Cheng TH5, Liu ZM6, Shen PC7, Huang CC8, Leung YM9.

Pharmacol Rep. 2014 Aug;66(4):576-84.

1Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan.and

2Division of Cardiology, Department of Medicine, Taipei Medical University Wan Fang Hospital, Taipei, Taiwan.and

3Graduate Institute of Neural and Cognitive Sciences, China Medical University, Taichung, Taiwan.and

4Department of Physiology, China Medical University, Taichung, Taiwan.and

5Department of Biological Sciences and Technology, China Medical University, Taichung, Taiwan.and

6Department of Cardiovascular Surgery, Shanghai East Hospital, Tongji University, Shanghai, China.and

7Department of Cardiology, Shanghai East Hospital, Tongji University, Shanghai, China.and

8Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan. Electronic address: [email protected]

9Graduate Institute of Neural and Cognitive Sciences, China Medical University, Taichung, Taiwan. Electronic address: [email protected]

 

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 2{Alpha} (peIF2{Alpha}) 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.

Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

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