Proteomic analysis of dopamine and α-synuclein interplay in a cellular model of Parkinson's disease pathogenesis.
Altered dopamine homeostasis is an accepted mechanism in the pathogenesis of Parkinson's disease. α-Synuclein overexpression and impaired disposal contribute to this mechanism. However, biochemical alterations associated with the interplay of cytosolic dopamine and increased α-synuclein are still unclear. Catecholaminergic SH-SY5Y human neuroblastoma cells are a suitable model for investigating dopamine toxicity. In the present study, we report the proteomic pattern of SH-SY5Y cells overexpressing α-synuclein (1.6-fold induction) after dopamine exposure. Dopamine itself is able to upregulate α-synuclein expression. However, the effect is not observed in cells that already overexpress α-synuclein as a consequence of transfection. The proteomic analysis highlights significant changes in 23 proteins linked to specific cellular processes, such as cytoskeleton structure and regulation, mitochondrial function, energetic metabolism, protein synthesis, and neuronal plasticity. A bioinformatic network enrichment procedure generates a significant model encompassing all proteins and allows us to enrich functional categories associated with the combination of factors analyzed in the present study (i.e. dopamine together with α-synuclein). In particular, the model suggests a potential involvement of the nuclear factor kappa B pathway that is experimentally confirmed. Indeed, α-synuclein significantly reduces nuclear factor kappa B activation, which is completely quenched by dopamine treatment.
Department of Structural and Functional Biology, University of Insubria, Busto Arsizio, Italy.
Tiziana
T
Alberio
Alessandra Maria
AM
Bossi
Alberto
A
Milli
Elisa
E
Parma
Marzia Bruna
MB
Gariboldi
Giovanna
G
Tosi
Leonardo
L
Lopiano
Mauro
M
Fasano
D002460:Cell Line; D004298:Dopamine / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D053858:Metabolic Networks and Pathways; D008959:Models, Neurological; D016328:NF-kappa B / Q000378:metabolism; D010300:Parkinson Disease / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics; D053719:Tandem Mass Spectrometry; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*
D016328:NF-kappa B; D051844:alpha-Synuclein; D004298:Dopamine