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

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

Journal of advanced research (2020-02-20)
Noela Rodríguez-Losada, Javier de la Rosa, María Larriva, Rune Wendelbo, José A Aguirre, Javier S Castresana, Santiago J Ballaz
ABSTRACT

Alpha-Synuclein (aSyn) is a chameleon-like protein. Its overexpression and intracellular deposition defines neurodegenerative α-synucleinopathies including Parkinson's disease. Whether aSyn up-regulation is the cause or the protective reaction to α-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 MTT 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. High-aSyn overexpression conferred to the carcinogenic neurons heightened tumorigenicity and resistance to senescence compared to low-aSyn cells, thus pointing to an inadequate level of aSyn stimulation, rather than the aSyn overload itself, as one of the factors contributing to α-synucleinopathy.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Synuclein α Antibody, Chemicon®, from rabbit
Sigma-Aldrich
Anti-Ki-67 Antibody, Chemicon®, from rabbit