MPP+ increases α-synuclein expression and ERK/MAP-kinase phosphorylation in human neuroblastoma SH-SY5Y cells

被引:132
作者
Gómez-Santos, C
Ferrer, I
Reiriz, J
Viñals, F
Barrachina, M
Ambrosio, S
机构
[1] Univ Barcelona, Dept Ciencias Fisiol 2, Unitat Bioquim, E-08907 Barcelona, Spain
[2] Univ Barcelona, Dept Biol Cellular & Anat Patol, Unitat Neuropatol, Barcelona, Spain
[3] Univ Barcelona, Escola Univ Infermeria, Dept Infermeria Fonamental & Medicoquirurg, Barcelona, Spain
关键词
Parkinson's disease; MPP+; alpha-synuclein MAP kinase; SH-SY5Y;
D O I
10.1016/S0006-8993(02)02422-8
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
(x-Synuclein is a bra-in presynaptic protein that is linked to familiar early onset Parkinson's disease and it is also a major component of Lewy bodies in sporadic Parkinson's disease and other neurodegenerative disorders. alpha-Synuclein expression increases in substantia nigra of both MPTP-treated rodents and non-human primates, used as animal models of parkinsonism. Here we describe an increase in (x-synuclein expression in a human neuroblastoma cell line, SH-SY5Y, caused by 5-100 muM MPP+, the active metabolite of MPTP which induces apoptosis in SH-SY5Y cells after a 4-day treatment. We also analysed the activation of the MAPK family, which is involved in several cellular responses to toxins and stressing conditions. Parallel to the increase in alpha-synuclein expression we observed activation of MEK1,2 and ERK/MAPK but not of SAPK/JNK or p38 kinase, The inhibition of the ERK/MAPK pathway with U0126, however, did not affect the increase in alpha-synuclein. The highest increase in a-synuclein (more than threefold) in 4-day cultures was found in adherent cells treated with low concentrations of MPP+ (5 muM). Inhibition of ERK/MAPK reduced the damage caused by MPP+. We suggest that alpha-synuclein increase and ERK/MAPK activation have a prominent role in the cell mechanisms of rescue and damage, respectively, after MPP+-treatment. (C) 2002 Elsevier Science BY. All rights reserved.
引用
收藏
页码:32 / 39
页数:8
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