Resveratrol protects SH-SY5Y neuroblastoma cells from apoptosis induced by dopamine.
- Author:
Mi Kyung LEE
1
;
Soon Ja KANG
;
Mortimer PONCZ
;
Ki Joon SONG
;
Kwang Sook PARK
Author Information
1. Department of Genetics, College of Life Science, Ewha Womans University, Seoul 120-750, Korea.
- Publication Type:Original Article
- Keywords:
antioxidant;
apoptosis;
dopamine;
neuroblastoma;
neurodegenerative diseases;
resveratrol
- MeSH:
Antioxidants/*pharmacology;
*Apoptosis;
Caspase 3/metabolism;
Cell Line, Tumor;
Cell Survival/drug effects;
Cytoprotection;
Dopamine/*physiology/toxicity;
Humans;
Membrane Potential, Mitochondrial/drug effects;
Poly(ADP-ribose) Polymerases/metabolism;
Proto-Oncogene Proteins c-bcl-2/metabolism;
Stilbenes/*pharmacology
- From:Experimental & Molecular Medicine
2007;39(3):376-384
- CountryRepublic of Korea
- Language:English
-
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.
