Soluble oligomers of amyloid-β peptide induce neuronal apoptosis by activating a cPLA2-dependent sphingomyelinase-ceramide pathway

被引:176
作者
Malaplate-Armand, Catherine [1 ]
Florent-Bechard, Sabrina [1 ]
Youssef, Ihsen [1 ]
Koziel, Violette [1 ]
Sponne, Isabelle [1 ]
Kriem, Badreddine [1 ]
Leininger-Muller, Brigitte [1 ]
Olivier, Jean-Luc [1 ]
Oster, Thierry [1 ]
Pillot, Thierry [1 ]
机构
[1] INPL, Lab Med & Therapeut Med, F-54505 Vandoeuvre Les Nancy, France
关键词
Alzheimer's disease; soluble amyloid-beta oligomers; cytosolic phospholipase A2; sphingomyelinases and apoptosis;
D O I
10.1016/j.nbd.2006.02.010
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Recent data have revealed that soluble oligomeric amyloid-beta peptide (A beta) may be the proximate effectors of neuronal injuries and death in Alzheimer's disease (AD) by unknown mechanisms. Consistently, we recently demonstrated the critical role of a redox-sensitive cytosolic calcium-dependent phospholipase A(2) (cPLA(2))-arachidonic acid (AA) pathway in A oligomer-induced cell death. According to the involvement of oxidative stress and polyunsaturated fatty acids like AA in the regulation of sphingomyelinase (SMase) activity, the present study underlines the role of SMases in soluble A beta-induced apoptosis. Soluble A beta oligomers induced the activation of both neutral and acidic SMases, as demonstrated by the direct measurement of their enzymatic activities, by the inhibitory effects of both specific neutral and acidic SMase inhibitors, and by gene knockdown using antisense oligonucleotides. Furthermore, soluble A beta-mediated activation of SMases and subsequent cell death were found to be inhibited by antioxidant molecules and a cPLA(2)-specific inhibitor or antisense oligonucleotide. We also demonstrate that sphingosine-1-phosphate is a potent neuroprotective factor against soluble A oligomer-induced cell death and apoptosis by inhibiting soluble A beta-induced activation of acidic sphingomyelinase. These results suggest that A beta oligomers induce neuronal death by activating neutral and acidic SMases in a redox-sensitive cPLA(2)-AA pathway. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:178 / 189
页数:12
相关论文
共 87 条
[1]   Changes in thiol content and expression of glutathione redox system genes in the hippocampus and cerebellum in Alzheimer's disease [J].
Aksenov, MY ;
Markesbery, WR .
NEUROSCIENCE LETTERS, 2001, 302 (2-3) :141-145
[2]   Sphingosine 1-phosphate-induced cell proliferation, survival, and related signaling events mediated by G protein-coupled receptors Edg3 and Edg5 [J].
An, SZ ;
Zheng, YH ;
Bleu, T .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (01) :288-296
[3]   DNA damage and apoptosis in Alzheimer's disease: Colocalization with c-Jun immunoreactivity, relationship to brain area, and effect of postmortem delay [J].
Anderson, AJ ;
Su, JH ;
Cotman, CW .
JOURNAL OF NEUROSCIENCE, 1996, 16 (05) :1710-1719
[4]   Molecular analysis of acid ceramidase deficiency in patients with Farber disease [J].
Bär, J ;
Linke, T ;
Ferlinz, K ;
Neumann, U ;
Schuchman, EH ;
Sandhoff, K .
HUMAN MUTATION, 2001, 17 (03) :199-209
[5]  
Billis W, 1998, RECENT PROG HORM RES, V53, P85
[6]   Nerve growth factor-induced p75-mediated death of cultured hippocampal neurons is age-dependent and transduced through ceramide generated by neutral sphingomyelinase [J].
Brann, AB ;
Tcherpakov, M ;
Williams, IM ;
Futerman, AH ;
Fainzilber, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (12) :9812-9818
[7]  
Brugg B, 1996, J NEUROCHEM, V66, P733
[8]   The critical role of methionine 35 in Alzheimer's amyloid-β-peptide (1-42)-induced oxidative stress and neurotoxicity [J].
Butterfield, DA ;
Boyd-Kimball, D .
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, 2005, 1703 (02) :149-156
[9]   Amyloid β-peptide [1-42]-associated free radical-induced oxidative stress and neurodegeneration in Alzheimer's disease grain:: Mechanisms and consequences [J].
Butterfield, DA .
CURRENT MEDICINAL CHEMISTRY, 2003, 10 (24) :2651-2659
[10]   Femtomole immunodetection of synthetic and endogenous amyloid-β oligomers and its application to Alzheimer's disease drug candidate screening [J].
Chang, L ;
Bakhos, L ;
Wang, ZQ ;
Venton, DL ;
Klein, WL .
JOURNAL OF MOLECULAR NEUROSCIENCE, 2003, 20 (03) :305-313