Galantamine prevents apoptosis induced by β-amyloid and thapsigargin:: involvement of nicotinic acetylcholine receptors

被引:132
|
作者
Arias, E
Alés, E
Gabilan, NH
Cano-Abad, MF
Villarroya, M
García, AG
López, MG
机构
[1] Univ Autonoma Madrid, Fac Med, Dept Farmacol, Inst Teofilo Hernando, E-28029 Madrid, Spain
[2] Univ Fed Santa Catarina, Dept Bioquim, BR-88049 Florianopolis, SC, Brazil
[3] Univ Madrid, Hosp Princesa, Inst Gerontol, E-28006 Madrid, Spain
[4] Serv Farmacol Clin, E-28006 Madrid, Spain
关键词
galantamine; nicotinic receptors; Bcl-2; neuroprotection; thapsigargin; beta-amyloid; apoptosis;
D O I
10.1016/S0028-3908(03)00317-4
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Galantamine is currently used to treat Alzheimer's disease patients; it behaves as a mild blocker of acetylcholinesterase (AChE) and has an allosteric modulating action on nicotinic acetylcholine receptors (nAChRs). In this study, we observed that galantamine prevented cell death induced by the peptide beta-amyloid(1-40) and thapsigargin in the human neuroblastoma cell line SH-SY5Y, as well as in bovine chromaffin cells. The protective effect of galantamine was concentration-dependent in both cell types; maximum protection was produced at 300 nM. The antiapoptotic effect of galantamine at 300 nM, against beta-amyloid(1-40) or thapsigargin-induced toxicity, was reversed by alpha-bungarotoxin. At neuroprotective concentrations, galantamine caused a mild and sustained elevation of the cytosolic concentration of calcium, [Ca2+](c), measured in single cells loaded with Fura-2. Incubation of the cells for 48 h with 300 nM galantamine doubled the density of alpha7 nicotinic receptors and tripled the expression of the antiapoptotic protein Bcl-2. These results strongly suggest that galantamine can prevent apoptotic cell death by inducing neuroprotection through a mechanism related to that described for nicotine, i.e. activation of nAChRs and upregulation of Bcl-2. These findings might explain the long-term beneficial effects of galantamine in patients suffering of Alzheimer's disease. (C) 2003 Elsevier Ltd. All rights reserved.
引用
收藏
页码:103 / 114
页数:12
相关论文
共 50 条
  • [11] Galantamine Enhances Dopaminergic Neurotransmission In Vivo Via Allosteric Potentiation of Nicotinic Acetylcholine Receptors
    Björn Schilström
    Vladimir B Ivanov
    Charlotte Wiker
    Torgny H Svensson
    Neuropsychopharmacology, 2007, 32 : 43 - 53
  • [12] Changes in nicotinic acetylcholine receptors under Alzheimer's disease conditions protection by galantamine
    Garcao, P.
    Oliveira, C. R.
    Agostinho, P.
    JOURNAL OF NEUROCHEMISTRY, 2007, 102 : 103 - 103
  • [13] Activation of α7 Nicotinic Acetylcholine Receptors Prevents Monosodium Iodoacetate-Induced Osteoarthritis in Rats
    Liu, Yuan
    Wu, Dongying
    Song, Fanglong
    Zhu, Chenlei
    Hui, Yujian
    Zhu, Qingcheng
    Wu, Jie
    Fan, Weimin
    Hu, Jun
    CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2015, 35 (02) : 627 - 638
  • [14] Inhibition of α9α10 nicotinic acetylcholine receptors prevents chemotherapy-induced neuropathic pain
    Romero, Haylie K.
    Christensen, Sean B.
    Mannelli, Lorenzo Di Cesare
    Gajewiak, Joanna
    Ramachandra, Renuka
    Elmslie, Keith S.
    Vetter, Douglas E.
    Ghelardini, Carla
    Iadonato, Shawn P.
    Mercado, Jose L.
    Olivera, Baldomera M.
    McIntosh, J. Michael
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2017, 114 (10) : E1825 - E1832
  • [15] α7 nicotinic acetylcholine receptors mediate β-amyloid peptide-induced tau protein phosphorylation
    Wang, HY
    Li, WW
    Benedetti, NJ
    Lee, DHS
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (34) : 31547 - 31553
  • [16] Galantamine activates muscle-type nicotinic acetylcholine receptors without binding to the acetylcholine-binding site
    Akk, G
    Steinbach, JH
    JOURNAL OF NEUROSCIENCE, 2005, 25 (08): : 1992 - 2001
  • [17] Involvement of nicotinic acetylcholine receptors in the regulation of microglial glutamate transporters
    Morioka, Norimitsu
    Nakata, Yoshihiro
    JOURNAL OF PHARMACOLOGICAL SCIENCES, 2012, 118 : 45P - 45P
  • [18] The Allosteric Potentiation of Nicotinic Acetylcholine Receptors by Galantamine Ameliorates the Cognitive Dysfunction in Beta Amyloid25–35 I.c.v.-Injected Mice: Involvement of Dopaminergic Systems
    Dayong Wang
    Yukihiro Noda
    Yuan Zhou
    Akihiro Mouri
    Hiroyuki Mizoguchi
    Atsumi Nitta
    Weiduo Chen
    Toshitaka Nabeshima
    Neuropsychopharmacology, 2007, 32 : 1261 - 1271
  • [19] Stimulation of α4β2 nicotinic acetylcholine receptors inhibits β-amyloid toxicity
    Kihara, T
    Shimohama, S
    Urushitani, M
    Sawada, H
    Kimura, J
    Kume, T
    Maeda, T
    Akaike, A
    BRAIN RESEARCH, 1998, 792 (02) : 331 - 334
  • [20] ETHANOL-INDUCED LOCOMOTOR-ACTIVITY - INVOLVEMENT OF CENTRAL NICOTINIC ACETYLCHOLINE-RECEPTORS
    BLOMQVIST, O
    SODERPALM, B
    ENGEL, JA
    BRAIN RESEARCH BULLETIN, 1992, 29 (02) : 173 - 178