alpha-Synuclein protects SH-SY5Y cells from dopamine toxicity.
Dopaminergic human neuroblastoma SH-SY5Y cells were stably transformed to increase expression of alpha-synuclein, a Parkinson's disease-related protein. Transformed cells were more resistant to oxidative insults, showing a cytoprotective role of alpha-synuclein. The expression of redox chaperonins (DJ-1, HSP70, and 14-3-3) was evaluated by Western blotting. Expression of alpha-synuclein reduced HSP70 levels even in the presence of dopamine, with a twofold increase of DJ-1 in the absence of oxidants. DJ-1 is significantly reduced by dopamine, and even more by dopamine and Cu(II). Increased alpha-synuclein expression did not affect 14-3-3, although dopamine increased its level by 60% in wild-type cells. alpha-Synuclein not only upregulated DJ-1, but also shifted all DJ-1 forms to a single spot at pI=5.7 not observed in wild-type cells. Dopamine gradually restored the distribution of DJ-1 forms to a situation similar to wild-type cells, with the form at pI=6.1 progressively enriched under oxidative conditions.
Colapinto
Monica
M
Department of Structural and Functional Biology, and Centre of Neuroscience, University of Insubria, Via Alberto da Giussano 12, 21052 Busto Arsizio, VA, Italy.
Mila
Silvia
S
Giraudo
Sabrina
S
Stefanazzi
Paola
P
Molteni
Monica
M
Rossetti
Carlo
C
Bergamasco
Bruno
B
Lopiano
Leonardo
L
Fasano
Mauro
M
D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D004298:Dopamine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D006801:Humans; D009447:Neuroblastoma / Q000473:pathology*; D051844:alpha-Synuclein / Q000008:administration & dosage*
D004338:Drug Combinations; D051844:alpha-Synuclein; D004298:Dopamine