MPP+ increases α-synuclein expression and ERK/MAP-kinase phosphorylation in human neuroblastoma SH-SY5Y cells
2002; Elsevier BV; Volume: 935; Issue: 1-2 Linguagem: Inglês
10.1016/s0006-8993(02)02422-8
ISSN1872-6240
AutoresCristina Gómez-Santos, Isidró Ferrer, J. Reiriz, Francesc Viñals, Marta Barrachina, Santiago Ambrosio,
Tópico(s)Neurological diseases and metabolism
Resumoα-Synuclein is a brain 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. α-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 α-synuclein expression in a human neuroblastoma cell line, SH-SY5Y, caused by 5–100 μM 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 α-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 α-synuclein. The highest increase in α-synuclein (more than threefold) in 4-day cultures was found in adherent cells treated with low concentrations of MPP+ (5 μM). Inhibition of ERK/MAPK reduced the damage caused by MPP+. We suggest that α-synuclein increase and ERK/MAPK activation have a prominent role in the cell mechanisms of rescue and damage, respectively, after MPP+-treatment.
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