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Dopamine (DA) is an oxidant that may contribute to the degeneration of dopaminergic neurons. The present study demonstrates that DA-induced cytotoxicity in human-derived neurotypic cells, SH-SY5Y, is prevented by resveratrol, one of the major antioxidative constituents found in the skin of grapes. SH-SY5Y cells, a neuroblastoma cell line, treated with DA at 300 and 500 M for 24 h underwent apoptotic death as determined by characteristic morphological features, including nuclear conden-sation, and loss of mitochondrial membrane poten-tial (MMP). Flow cytometric analysis using Annexin V showed that DA can induce significant and severe apoptosis. Exposure to resveratrol (5 M) for 1 h prior to the DA treatment attenuated DA-induced cyto-toxicity, and rescued the loss of MMP. To investigate the apoptotic signaling pathways relevant to the restoration of DA-induced apoptosis by resveratrol, we carried out quantitative analysis of Bcl-2, cas-pase-3, and cleaved poly ADP-ribose polymerase (PARP) by immunoblot analysis. Resveratrol pre-treatment led to a decrease in cleavage of PARP, an increase in the Bcl-2 protein, and activation of cas-pase-3. These results suggest that DA may be a potential oxidant of neuronal cells at biologically relevant concentrations. Resveratrol may protect SH-SY5Y cells against this cytotoxicity, reducing intracellular oxidative stress through canonical signal pathways of apoptosis and may be of bio-logical importance in the prevention of a dopami-nergic neurodegenerative disorder such as Parkin-son disease.

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