N-methyl-D-aspartate receptor-mediated calcium overload and endoplasmic reticulum stress are involved in interleukin-1beta-induced neuronal apoptosis in rat hippocampus

被引:46
作者
Dong, Yilong [1 ,5 ]
Kalueff, Allan V. [2 ,6 ,7 ]
Song, Cai [2 ,3 ,4 ]
机构
[1] Yunnan Univ, Sch Med, 2 Cuihu Bei Rd, Kunming 650091, Yunnan, Peoples R China
[2] Guangdong Ocean Univ, Coll Food Sci & Technol, Res Inst Marine Drugs & Nutr, Zhanjiang, Peoples R China
[3] China Med Univ, Coll Med, Grad Inst Biomed Sci, Shenyang, Peoples R China
[4] China Med Univ Hosp, Dept Med Res, Taichung 40402, Taiwan
[5] Univ Prince Edward Isl, Dept Biomed Sci, 550 Univ Ave, Charlottetown, PE C1A 4P3, Canada
[6] St Petersburg State Univ, Inst Translat Biomed, 7-9 Univ Embankment, St Petersburg, Russia
[7] Ural Fed Univ, Ekaterinburg 620002, Russia
关键词
Interleukin-lbeta; Microglia; NMDA receptor; Endoplasmic reticulum stress; Neurotoxicity; ALZHEIMERS-DISEASE; GLUTAMATE; RELEASE; NEURODEGENERATION; NEUROPROTECTION; MICROGLIA; RESPONSES; BLOCKADE; CHANNELS; PATHWAY;
D O I
10.1016/j.jneuroim.2017.03.005
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Increased levels of interleukin (IL)-1 beta and its gene expression are implicated in the etiology of Alzheimer's disease (AD). IL-1 beta activates microglia and stimulates glutamatergic N-methyl-D-aspartate receptor NMDA receptor expression, thereby disturbing intracellular Ca2+ homeostasis. Ca2+ disequilibrium, in turn, may trigger endoplasmic reticulum (ER) stress, contributing to overall excitotoxicity and neuronal death that evoke AD. However, it is unclear whether IL-1 beta-induced neuronal apoptosis is mediated by the glutamatergic system, ER stress and/or Ca2+ dysfunction. The present study investigated the role of NMDA receptor (NMDAR) in ER stress and IL-1 beta-evoked neuronal death by assessing NMDAR-induced Ca2+ overload and NMDA-mediated ER stress. Male Long Evans rats were treated with IL-1 beta (with or without NMDAR antagonist MK801) injected intracerebroventricularly for 8 days. Glutamate concentration was measured by HPLC, and mRNA and protein expression of microglial biomarkers and NMDAR, as well as markers of Ca2+ overload (caplain2) and ER stress (glucose-regulated protein 78, GRP78, and C/EBP homologous protein-10, CHOP), were assessed by real-time PCR and western blot. Apoptosis was also evaluated in the hippocampal neurons using TUNEL Overall, IL-1 beta induced robust neuronal apoptosis, accompanied by upregulated NMDAR, caplain2, GRP78 and CHOP. MK801 pretreatment significantly attenuated neuronal apoptosis and NMDA up-regulation, also reducing GRP78 and CHOP expression. In summary, these results suggest that IL-1 beta may disturb intracellular Ca2+ homeostasis via NMDAR-mediated mechanism, thereby triggering neuronal apoptosis by enhancing ER stress. (C) 2017 Elsevier B.V. All rights reserved.
引用
收藏
页码:7 / 13
页数:7
相关论文
共 28 条
[1]   NMDA receptors Recent insights and clinical correlations [J].
Benarroch, Eduardo E. .
NEUROLOGY, 2011, 76 (20) :1750-1757
[2]   Therapeutic Targeting of the Endoplasmic Reticulum in Alzheimer's Disease [J].
Chadwick, Wayne ;
Mitchell, Nicholas ;
Martin, Bronwen ;
Maudsley, Stuart .
CURRENT ALZHEIMER RESEARCH, 2012, 9 (01) :110-119
[3]   Excitatory glycine receptors containing the NR3 family of NMDA receptor subunits [J].
Chatterton, JE ;
Awobuluyi, M ;
Premkumar, LS ;
Takahashi, H ;
Talantova, M ;
Shin, Y ;
Cui, JK ;
Tu, SC ;
Kevin, ASK ;
Nakanishi, N ;
Tong, G ;
Lipton, SA ;
Zhang, DX .
NATURE, 2002, 415 (6873) :793-798
[4]   Cab45S inhibits the ER stress-induced IRE1-JNK pathway and apoptosis via GRP78/BiP [J].
Chen, L. ;
Xu, S. ;
Liu, L. ;
Wen, X. ;
Xu, Y. ;
Chen, J. ;
Teng, J. .
CELL DEATH & DISEASE, 2014, 5 :e1219-e1219
[5]   Linking cocaine to endoplasmic reticulum in striatal neurons: Role of glutamate receptors [J].
Choe, Eun Sang ;
Ahn, Sung Min ;
Yang, Ju Hwan ;
Go, Bok Soon ;
Wang, John Q. .
BASAL GANGLIA, 2011, 1 (02) :59-63
[6]   The Cell Biology of the Unfolded Protein Response [J].
Diehl, J. Alan ;
Fuchs, Serge Y. ;
Koumenis, Costantinos .
GASTROENTEROLOGY, 2011, 141 (01) :38-U109
[7]   Interleukin-1 receptor antagonist inhibits the release of glutamate, hydroxyl radicals, and prostaglandin E2 in the hypothalamus during pyrogen-induced fever in rabbits [J].
Huang, Kuo-Feng ;
Huang, Wu-Tein ;
Lin, Kao-Chang ;
Lin, Mao-Tsun ;
Chang, Ching-Ping .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2010, 629 (1-3) :125-131
[8]   Methamphetamine induces neuronal apoptosis via cross-talks between endoplasmic reticulum and mitochondria-dependent death cascades [J].
Jayanthi, S ;
Deng, XL ;
Noailles, PAH ;
Ladenheim, B ;
Cadet, JL .
FASEB JOURNAL, 2004, 18 (02) :238-251
[9]   Evidence that pregabalin reduces neuropathic pain by inhibiting the spinal release of glutamate [J].
Kumar, Naresh ;
Laferriere, Andre ;
Yu, Jonathan S. C. ;
Leavitt, Amelia ;
Coderre, Terence J. .
JOURNAL OF NEUROCHEMISTRY, 2010, 113 (02) :552-561
[10]  
Lee JK, 2002, MOL CELLS, V14, P339