Exp Mol Med.
2007 Jun;39(3):376-384.
Resveratrol protects SH-SY5Y neuroblastoma cells from apoptosis induced by dopamine
- Affiliations
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- 1Department of Genetics, College of Life Science, Ewha Womans University, Seoul 120-750, Korea.
- 2Department of Science Education, College of Education, Ewha Womans University, Seoul 120-750, Korea.
- 3Division of Hematology, Children's Hospital of Philadelphia, PA 19104, USA.
- 4Department of Microbiology and Bank for Pathogenic Viruses, Division of Brain Korea 21 Program for Biomedical Science, College of Medicine, Korea University, Seoul 136-705, Korea. parkbcmb@korea.ac.kr
Abstract
- 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 micrometer for 24 h underwent apoptotic death as determined by characteristic morphological features, including nuclear condensation, and loss of mitochondrial membrane potential (MMP). Flow cytometric analysis using Annexin V showed that DA can induce significant and severe apoptosis. Exposure to resveratrol (5 micrometer) for 1 h prior to the DA treatment attenuated DA-induced cytotoxicity, 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, caspase-3, and cleaved poly ADP-ribose polymerase (PARP) by immunoblot analysis. Resveratrol pretreatment led to a decrease in cleavage of PARP, an increase in the Bcl-2 protein, and activation of caspase-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 biological importance in the prevention of a dopaminergic neurodegenerative disorder such as Parkinson disease.
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