Beta-amyloid causes downregulation of calcineurin in neurons through induction of oxidative stress

被引:50
作者
Celsi, F. [1 ]
Svedberg, M.
Unger, C.
Cotman, C. W.
Carri, M. T.
Ottersen, O. P.
Nordberg, A.
Torp, R.
机构
[1] Univ Oslo, Lab Mol Neurosci, Ctr Mol Biol & Neurosci, Oslo, Norway
[2] Fdn Santa Lucia IRCCS, I-00179 Rome, Italy
[3] Univ Roma Tor Vergata, Dept Biol, Rome, Italy
[4] Karolinska Inst, Div Mol Neuropharmacol, Stockholm, Sweden
[5] Univ Calif Irvine, Inst Brain Aging & Dementia, Irvine, CA USA
关键词
D O I
10.1016/j.nbd.2006.12.022
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Calcineurin is an abundant cytosolic protein that is implicated in the modulation of glutamate release. Here we show that the expression level of this enzyme is reduced in primary neuronal cultures treated with beta-amyloid. Parallel experiments in ETNA cell lines expressing SOD1 suggested that the effect of beta-amyloid on calcineurin expression is mediated by oxidative stress. The relevance of the in vitro experiments was assessed by analysis of tissue from patients with Alzheimer's disease (AD) and tissue from two strains of transgenic mice that mimic aspects of AD. The tissue from the AD brains displayed a pronounced downregulation of calcineurin immunoreactivity in profiles that were negative for glial fibrillary acidic protein (GFAP). In the hippocampus of the transgenic animals (which were analyzed in an early stage of the disease) the downregulation of calcineurin was restricted to mossy fiber terminals. A downregulation of the presynaptic pool of calcineurin may contribute to the dysregulation of glutamate release that is considered a hallmark of AD. (c) 2007 Elsevier Inc. All rights reserved.
引用
收藏
页码:342 / 352
页数:11
相关论文
共 45 条
[1]   Decreased activity and increased aggregation of brain calcineurin during aging [J].
Agbas, A ;
Zaidi, A ;
Michaelis, EK .
BRAIN RESEARCH, 2005, 1059 (01) :59-71
[2]   Acetylcholinesterase promotes the aggregation of amyloid-beta-peptide fragments by forming a complex with the growing fibrils [J].
Alvarez, A ;
Opazo, C ;
Alarcon, R ;
Garrido, J ;
Inestrosa, NC .
JOURNAL OF MOLECULAR BIOLOGY, 1997, 272 (03) :348-361
[3]  
Beeri R, 1997, J NEUROCHEM, V69, P2441
[4]   TRANSGENIC EXPRESSION OF HUMAN ACETYLCHOLINESTERASE INDUCES PROGRESSIVE COGNITIVE DETERIORATION IN MICE [J].
BEERI, R ;
ANDRES, C ;
LEVLEHMAN, E ;
TIMBERG, R ;
HUBERMAN, T ;
SHANI, M ;
SOREQ, H .
CURRENT BIOLOGY, 1995, 5 (09) :1063-1071
[5]   Proteomic identification of proteins oxidized by Aβ(1-42) in synaptosomes:: Implications for Alzheimer's disease [J].
Boyd-Kimball, D ;
Castegna, A ;
Sultana, R ;
Poon, HF ;
Petroze, R ;
Lynn, BC ;
Klein, JB ;
Butterfield, DA .
BRAIN RESEARCH, 2005, 1044 (02) :206-215
[6]   The metallobiology of Alzheimer's disease [J].
Bush, AI .
TRENDS IN NEUROSCIENCES, 2003, 26 (04) :207-214
[7]   Cu,Zn-superoxide dismutase-dependent apoptosis induced by nitric oxide in neuronal cells [J].
Ciriolo, MR ;
De Martino, A ;
Lafavia, E ;
Rossi, L ;
Carrí, MT ;
Rotilio, G .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (07) :5065-5072
[8]   Identification of the kainate receptor subunits underlying modulation of excitatory synaptic transmission in the CA3 region of the hippocampus [J].
Contractor, A ;
Swanson, GT ;
Sailer, A ;
O'Gorman, S ;
Heinemann, SF .
JOURNAL OF NEUROSCIENCE, 2000, 20 (22) :8269-8278
[9]   The dephosphins: dephosphorylation by calcineurin triggers synaptic vesicle endocytosis [J].
Cousin, MA ;
Robinson, PJ .
TRENDS IN NEUROSCIENCES, 2001, 24 (11) :659-665
[10]   Coassembly of two GluR6 Kainate receptor splice variants within a functional protein complex [J].
Coussen, F ;
Perrais, D ;
Jaskolski, F ;
Sachidhanandam, S ;
Normand, E ;
Bockaert, J ;
Marin, P ;
Mulle, C .
NEURON, 2005, 47 (04) :555-566