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 journalArticle

3 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

Fingerprint

Purinergic P2X7 Receptors
Taurine
Endoplasmic Reticulum Stress
Reactive Oxygen Species
Cell Death
Caspase 3
Transcription Factor CHOP
Eukaryotic Initiation Factor-2
Eukaryotic Initiation Factors
Fura-2
Mitochondrial Membrane Potential
Neuroprotective Agents
Neuroprotection
Endoplasmic Reticulum
Western Blotting
Cell Line
Acids
3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate

Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Medicine(all)

Cite this

Protection of differentiated neuronal NG108-15 cells from P2X7 receptor-mediated toxicity by taurine. / Chao, Chia Chia; Chan, Paul; Kuo, Chang Shin; Gong, Chi Li; Cheng, Tzu-Hurng; Liu, Zhong Min; Shen, Pei Chen; Huang, Chieh Chen; Leung, Yuk Man.

In: Pharmacological Reports, Vol. 66, No. 4, 2014, p. 576-584.

Research output: Contribution to journalArticle

Chao, CC, Chan, P, Kuo, CS, Gong, CL, Cheng, T-H, Liu, ZM, Shen, PC, Huang, CC & Leung, YM 2014, 'Protection of differentiated neuronal NG108-15 cells from P2X7 receptor-mediated toxicity by taurine', Pharmacological Reports, vol. 66, no. 4, pp. 576-584. https://doi.org/10.1016/j.pharep.2014.01.005
Chao, Chia Chia ; Chan, Paul ; Kuo, Chang Shin ; Gong, Chi Li ; Cheng, Tzu-Hurng ; Liu, Zhong Min ; Shen, Pei Chen ; Huang, Chieh Chen ; Leung, Yuk Man. / Protection of differentiated neuronal NG108-15 cells from P2X7 receptor-mediated toxicity by taurine. In: Pharmacological Reports. 2014 ; Vol. 66, No. 4. pp. 576-584.
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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.",
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T1 - Protection of differentiated neuronal NG108-15 cells from P2X7 receptor-mediated toxicity by taurine

AU - Chao, Chia Chia

AU - Chan, Paul

AU - Kuo, Chang Shin

AU - Gong, Chi Li

AU - Cheng, Tzu-Hurng

AU - Liu, Zhong Min

AU - Shen, Pei Chen

AU - Huang, Chieh Chen

AU - Leung, Yuk Man

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - ER stress

KW - Neurotoxicity

KW - NG108-15 cells

KW - Taurine

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