Detalle Publicación

Overexpression of alpha-synuclein promotes both cell proliferation and cell toxicity in human SH-SY5Y neuroblastoma cells

Autores: RodrIguez-Losada, N.; de la Rosa Fernández-Pacheco, Francisco Javier; Larriva Hormigos, María; Wendelbo, R.; Aguirre, J. A.; Sáez Castresana, Javier; Ballaz, S. J. (Autor de correspondencia)
ISSN: 2090-1232
Volumen: 23
Páginas: 37 - 45
Fecha de publicación: 2020
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.