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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

cDNA gene expression profile homology of antioxidants and their antiapoptotic and proapoptotic activities in human neuroblastoma cells.

Antioxidants have concentration-dependent neuroprotective and proapoptotic activities in models of Parkinson's disease. The aim of our study was to determine gene-protein pathways of the antioxidants, dopamine (DA), R-apomorphine (R-APO), melatonin, and green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG), in neuroblastoma cells, using a customized cDNA microarray and quantitative reverse transcriptase-polymerase chain reaction gene expression techniques. We demonstrate a concentration-dependent correlation between these compounds and modulation of cell survival/cell death-related gene pathways. High toxic concentration of DA (500 microM), R-APO (50 microM), melatonin (50 microM), and EGCG (50 microM) exhibited a similar profile of proapoptotic gene expression, increasing the level of bax, caspase-6, fas ligand, and the cell-cycle inhibitor gadd45 genes, while decreasing antiapoptotic bcl-2 and bcl-xL. Conversely, the low neuroprotective concentrations (1-10 microM) of these compounds induced an antiapoptotic response. Melatonin displayed an extremely low index of mortality, which may be partially explained by the observation that a high concentration did not significantly affect the expression of mitochondrial Bcl-2 family members, bcl-2 and bax. Protein analysis of Bcl-2, Bax, and activated caspase-3 correlated with the gene expression pattern. Our results provide for the first time new insights into the molecular events involved in the dose-dependent neuroprotective and neurotoxic activities of catechols and indole amine compounds.[1]

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