Accessibility navigation


Sulforaphane protects cortical neurons against 5-S-cysteinyl-dopamine-induced toxicity through the activation of ERK1/2, Nrf-2 and the upregulation of detoxification enzymes

Vauzour, D., Buonfiglio, M., Corona, G., Chirafisi, J., Vafeiadou, K., Angeloni, C., Hrelia, S., Hrelia, P. and Spencer, J. P. E. (2010) Sulforaphane protects cortical neurons against 5-S-cysteinyl-dopamine-induced toxicity through the activation of ERK1/2, Nrf-2 and the upregulation of detoxification enzymes. Molecular Nutrition & Food Research, 54 (4). pp. 532-542. ISSN 1613-4125

Full text not archived in this repository.

To link to this article DOI: 10.1002/mnfr.200900197

Abstract/Summary

The degeneration of dopaminergic neurons in the substantia nigra has been linked to the formation of the endogenous neurotoxin 5-S-cysteinyl-dopamine. Sulforaphane (SFN), an isothiocyanate derived from the corresponding precursor glucosinolate found in cruciferous vegetables has been observed to exert a range of biological activities in various cell populations. In this study, we show that SFN protects primary cortical neurons against 5-S-cysteinyl-dopamine induced neuronal injury. Pre-treatment of cortical neurons with SFN (0.01-1 microM) resulted in protection against 5-S-cysteinyl-dopamine-induced neurotoxicity, which peaked at 100 nM. This protection was observed to be mediated by the ability of SFN to modulate the extracellular signal-regulated kinase 1 and 2 and the activation of Kelch-like ECH-associated protein 1/NF-E2-related factor-2 leading to the increased expression and activity of glutathione-S-transferase (M1, M3 and M5), glutathione reductase, thioredoxin reductase and NAD(P)H oxidoreductase 1. These data suggest that SFN stimulates the NF-E2-related factor-2 pathway of antioxidant gene expression in neurons and may protect against neuronal injury relevant to the aetiology of Parkinson's disease.

Item Type:Article
Refereed:Yes
Divisions:Faculty of Life Sciences > School of Chemistry, Food and Pharmacy > Department of Food and Nutritional Sciences > Human Nutrition Research Group
Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR)
ID Code:18554
Uncontrolled Keywords:Animals; Cell Death/drug effects; Cells, Cultured; Cerebral Cortex/*cytology; Dopamine/*analogs & derivatives/toxicity; Enzyme Activation/drug effects; Extracellular Signal-Regulated MAP Kinases/*metabolism; Glutathione/analysis; Glutathione Reductase/metabolism; Glutathione Transferase/metabolism; Mice; Mitogen-Activated Protein Kinase 1/metabolism; Mitogen-Activated Protein Kinase 3/metabolism; NAD(P)H Dehydrogenase (Quinone)/metabolism; NF-E2-Related Factor 2/drug effects/*physiology; Neurons/*drug effects; Neuroprotective Agents/pharmacology; Phosphorylation/drug effects; Thiocyanates/*pharmacology; Thioredoxin-Disulfide Reductase/metabolism;
Additional Information:BB/C518222/1/Biotechnology and Biological Sciences Research Council/United Kingdom BB/G005702/1/Biotechnology and Biological Sciences Research Council/United Kingdom G0400278/Medical Research Council/United Kingdom Research Support, Non-U.S. Gov't Germany
Publisher:Wiley-Blackwell

University Staff: Request a correction | Centaur Editors: Update this record

Page navigation