Lycopene protects neuroblastoma cells against oxidative damage via depression of ER stress.

Lycopene is a pigment derived from tomatoes and other red fruits, and has potent antioxidant and antitumor effects. However, its potential role in alleviating oxidative damage in neuronal cells is not well defined. In this study, we investigated the effects of lycopene on H2O2-induced damage in neuroblastoma cells, as well as the underlying mechanisms. Exposure to H(2)O(2)markedly decreased the viability of SH-SY5Y cells and increased LDH release, both of which were reversed by lycopene pretreatment. Lycopene also ameliorated H2O2-induced damage and reduced the expression of apoptotic markers, such as Bcl-2, Bax, and cleaved caspase 3. In addition, the H2O2-induced oxidative markers, including MDA, 8-OHdG, and protein carbonyls, were also downregulated by lycopene. Exogenous H(2)O(2)activated the GRP78/PERK/eIF2 alpha signaling pathway, which was inhibited by pretreatment with lycopene. Finally, lycopene significantly ameliorated ER stress-induced activation and nuclear translocation of CHOP. Overexpression of CHOP markedly reversed the antiapoptotic effects of lycopene, indicating that it is essential for the latter's protective effects. Taken together, lycopene protects neuroblastoma cells from oxidative stress and ER stress-induced damage by inhibiting the PERK-CHOP signaling pathway, which is a potential therapeutic target in neurodegenerative diseases. Practical Application Lycopene demonstrated antioxidative damage properties in protecting the neural systemin vitro. The present study provides a novel preventive strategy against neurodegenerative diseases. Increased consumption of lycopene-based products and lycopene-rich fruits and vegetables may result in a lower risk for neurodegenerative diseases.