Altered dopamine homeostasis is an accepted mechanism in the pathogenesisof Parkinson’s disease. a-Synuclein overexpression and impaired disposalcontribute to this mechanism. However, biochemical alterationsassociated with the interplay of cytosolic dopamine and increased a-synucleinare still unclear. Catecholaminergic SH-SY5Y human neuroblastomacells are a suitable model for investigating dopamine toxicity. In the presentstudy, we report the proteomic pattern of SH-SY5Y cells overexpressinga-synuclein (1.6-fold induction) after dopamine exposure. Dopamineitself is able to upregulate a-synuclein expression. However, the effect isnot observed in cells that already overexpress a-synuclein as a consequenceof transfection. The proteomic analysis highlights significant changes in 23proteins linked to specific cellular processes, such as cytoskeleton structureand regulation, mitochondrial function, energetic metabolism, protein synthesis,and neuronal plasticity. A bioinformatic network enrichment proceduregenerates a significant model encompassing all proteins and allows usto enrich functional categories associated with the combination of factorsanalyzed in the present study (i.e. dopamine together with a-synuclein). Inparticular, the model suggests a potential involvement of the nuclear factorkappa B pathway that is experimentally confirmed. Indeed, a-synuclein significantlyreduces nuclear factor kappa B activation, which is completelyquenched by dopamine treatment.
Proteomic analysis of dopamine and α-synuclein interplay in a cellular model of Parkinson’s disease pathogenesis.
BOSSI, Alessandra Maria;
2010-01-01
Abstract
Altered dopamine homeostasis is an accepted mechanism in the pathogenesisof Parkinson’s disease. a-Synuclein overexpression and impaired disposalcontribute to this mechanism. However, biochemical alterationsassociated with the interplay of cytosolic dopamine and increased a-synucleinare still unclear. Catecholaminergic SH-SY5Y human neuroblastomacells are a suitable model for investigating dopamine toxicity. In the presentstudy, we report the proteomic pattern of SH-SY5Y cells overexpressinga-synuclein (1.6-fold induction) after dopamine exposure. Dopamineitself is able to upregulate a-synuclein expression. However, the effect isnot observed in cells that already overexpress a-synuclein as a consequenceof transfection. The proteomic analysis highlights significant changes in 23proteins linked to specific cellular processes, such as cytoskeleton structureand regulation, mitochondrial function, energetic metabolism, protein synthesis,and neuronal plasticity. A bioinformatic network enrichment proceduregenerates a significant model encompassing all proteins and allows usto enrich functional categories associated with the combination of factorsanalyzed in the present study (i.e. dopamine together with a-synuclein). Inparticular, the model suggests a potential involvement of the nuclear factorkappa B pathway that is experimentally confirmed. Indeed, a-synuclein significantlyreduces nuclear factor kappa B activation, which is completelyquenched by dopamine treatment.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.