Overexpression of alpha-synuclein promotes both cell proliferation and cell toxicity in human SH-SY5Y neuroblastoma cells
Keywords: 
Alpha-synuclein
SH-SY5Y cells
Rotenone
Graphene oxide
Parkinson's disease
Cell senescence
Issue Date: 
2020
ISSN: 
2090-1232
Note: 
CC BY NC ND
Citation: 
Rodríguez-Losada, N. (Noela); Rosa-Fernández-Pacheco, F.J. (Francisco Javier) de la; Larriva-Hormigos, M. (María); et al. "Overexpression of alpha-synuclein promotes both cell proliferation and cell toxicity in human SH-SY5Y neuroblastoma cells". Journal of Advanced Research. 23, 2020, 37 - 45
Abstract
Alpha-Synuclein (aSyn) is a chameleon-like protein. Its overexpression and intracellular deposition defines neurodegenerative alpha-synucleinopathies including Parkinson's disease. Whether aSyn upregulation is the cause or the protective reaction to alpha-synucleinopathies remains unresolved. Remarkably, the accumulation of aSyn is involved in cancer. Here, the neuroblastoma SH-SY5Y cell line was genetically engineered to overexpress aSyn at low and at high levels. aSyn cytotoxicity was assessed by the MIT and vital-dye exclusion methods, observed at the beginning of the sub-culture of low-aSyn overexpressing neurons when cells can barely proliferate exponentially. Conversely, high-aSyn overexpressing cultures grew at high rates while showing enhanced colony formation compared to low-aSyn neurons. Cytotoxicity of aSyn overexpression was indirectly revealed by the addition of pro-oxidant rotenone. Pretreatment with partially reduced graphene oxide, an apoptotic agent, increased toxicity of rotenone in low-aSyn neurons, but, it did not in high-aSyn neurons. Consistent with their enhanced proliferation, high-aSyn neurons showed elevated levels of SMP30, a senescence-marker protein, and the mitosis Ki-67 marker.

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