Ca2+store depletion and endoplasmic reticulum stress are involved in P2X7 receptor-mediated neurotoxicity in differentiated NG108-15 cells

被引:33
作者
Chao, Chia-Chia [2 ]
Huang, Chieh-Chen [2 ]
Lu, Dah-Yuu [1 ]
Wong, Kar-Lok [3 ]
Chen, Yun-Ru [3 ]
Cheng, Tzu-Hurng [4 ]
Leung, Yuk-Man [1 ,2 ]
机构
[1] China Med Univ, Grad Inst Neural & Cognit Sci, Taichung 40402, Taiwan
[2] Natl Chung Hsing Univ, Dept Life Sci, Taichung 40227, Taiwan
[3] China Med Univ, Dept Anesthesiol, Taichung 40402, Taiwan
[4] China Med Univ, Dept Biol Sci & Technol, Taichung 40402, Taiwan
关键词
P2X7; RECEPTOR; Ca2+STORE; ENDOPLASMIC RETICULUM STRESS; SPINAL-CORD-INJURY; IMPROVES RECOVERY; P2X(7) RECEPTORS; CA2+ RELEASE; ER STRESS; IN-VITRO; STIMULATION; STORES; ATP; ASTROCYTES;
D O I
10.1002/jcb.24010
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
P2X7 receptor (P2X7R) activation by extracellular ATP triggers influx of Na+ and Ca2+, cytosolic Ca2+ overload and consequently cytotoxicity. Whether disturbances in endoplasmic reticulum (ER) Ca2+ homeostasis and ER stress are involved in P2X7R-mediated cell death is unknown. In this study, a P2X7R agonist (BzATP) was used to activate P2X7R in differentiated NG108-15 neuronal cells. In a concentration-dependent manner, application of BzATP (10100?mu M) immediately raised cytosolic Ca2+ concentration ([Ca2+]i) and caused cell death after a 24-h incubation. P2X7R activation for 2?h did not cause cell death but resulted in a sustained reduction in ER Ca2+ pool size, as evidenced by a diminished cyclopiazonic acid-induced Ca2+ discharge (fura 2 assay) and a lower fluorescent signal in cells loaded with Mag-fura 2 (ER-specific Ca2+-fluorescent dye). Furthermore, P2X7R activation (2?h) led to the appearance of markers of ER stress [phosphorylated a subunit of eukaryotic initiation factor 2 (p-eIF2a) and C/EBP homologous protein (CHOP)] and apoptosis (cleaved caspase 3). Xestospongin C (XeC), an antagonist of inositol-1,4,5-trisphosphate (IP3) receptor (IP3R), strongly inhibited BzATP-triggered [Ca2+]i elevation, suggesting that the latter involved Ca2+ release via IP3R. XeC pretreatment not only attenuated the reduction in Ca2+ pool size in BzATP-treated cells, but also rescued cell death and prevented BzATP-induced appearance of ER stress and apoptotic markers. These novel observations suggest that P2X7R activation caused not only Ca2+ overload, but also Ca2+ release via IP3R, sustained Ca2+ store depletion, ER stress and eventually apoptotic cell death. J. Cell. Biochem. 113: 13771385, 2012. (c) 2011 Wiley Periodicals, Inc.
引用
收藏
页码:1377 / 1385
页数:9
相关论文
共 33 条
[11]  
2-M
[12]   Stimulation of the P2X7 receptor kills rat retinal ganglion cells in vivo [J].
Hu, Huiling ;
Lu, Wennan ;
Zhang, Mei ;
Zhang, Xiulan ;
Argall, Arthur J. ;
Patel, Shaun ;
Lee, Ga Eun ;
Kim, Yong-Chul ;
Jacobson, Kenneth A. ;
Laties, Alan M. ;
Mitchell, Claire H. .
EXPERIMENTAL EYE RESEARCH, 2010, 91 (03) :425-432
[13]   ATP-gated P2X cation-channels [J].
Jarvis, Michael F. ;
Khakh, Baljit S. .
NEUROPHARMACOLOGY, 2009, 56 (01) :208-215
[14]   Multiplicity of Ca2+ messengers and Ca2+ stores:: A perspective from cyclic ADP-ribose and NAADP [J].
Lee, HC .
CURRENT MOLECULAR MEDICINE, 2004, 4 (03) :227-237
[15]   Calyculin A-induced endothelial cell shape changes are independent of [Ca2+]i elevation and may involve actin polymerization [J].
Leung, YM ;
Kwan, TK ;
Kwan, CY ;
Daniel, EE .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2002, 1589 (02) :93-103
[16]   Voltage-Gated K+ Channels Play a Role in cAMP-Stimulated Neuritogenesis in Mouse Neuroblastoma N2A Cells [J].
Leung, Yuk-Man ;
Huang, Chien-Fang ;
Chao, Chia-Chia ;
Lu, Dah-Yuu ;
Kuo, Chang-Shin ;
Cheng, Tzu-Hurng ;
Chang, Li-Yun ;
Chou, Chun-Hsiao .
JOURNAL OF CELLULAR PHYSIOLOGY, 2011, 226 (04) :1090-1098
[17]   Hypoxia-Induced Matrix Metalloproteinase-13 Expression in Astrocytes Enhances Permeability of Brain Endothelial Cells [J].
Lu, Dah-Yuu ;
Yu, Wei-Hsuan ;
Yeh, Wei-Lan ;
Tang, Chih-Hsin ;
Leung, Yuk-Man ;
Wong, Kar-Lok ;
Chen, Yuh-Fung ;
Lai, Chih-Ho ;
Fu, Wen-Mei .
JOURNAL OF CELLULAR PHYSIOLOGY, 2009, 220 (01) :163-173
[18]   Excitotoxic damage to white matter [J].
Matute, Carlos ;
Alberdi, Elena ;
Domercq, Maria ;
Sanchez-Gomez, Maria-Victoria ;
Perez-Samartin, Alberto ;
Rodriguez-Antiguedad, Alfredo ;
Perez-Cerda, Fernando .
JOURNAL OF ANATOMY, 2007, 210 (06) :693-702
[19]   Systemic administration of an antagonist of the ATP-sensitive receptor P2X7 improves recovery after spinal cord injury [J].
Peng, Weiguo ;
Cotrina, Maria L. ;
Han, Xiaoning ;
Yu, Hongmei ;
Bekar, Lane ;
Blum, Livnat ;
Takano, Takahiro ;
Tian, Guo-Feng ;
Goldman, Steven A. ;
Nedergaard, Maiken .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (30) :12489-12493
[20]   The nucleotide receptor P2X7 mediates actin reorganization and membrane blebbing in RAW 264.7 macrophages via p38 MAP kinase and Rho [J].
Pfeiffer, ZA ;
Aga, M ;
Prabhu, U ;
Watters, JJ ;
Hall, DJ ;
Bertics, PJ .
JOURNAL OF LEUKOCYTE BIOLOGY, 2004, 75 (06) :1173-1182