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, David ORCID: https://orcid.org/0000-0001-5952-8756, Buonfiglio, Maria, Corona, Giulia, Chirafisi, Joselita, Vafeiadou, Katerina, Angeloni, Cristina, Hrelia, Silvana, Hrelia, Patrizia and Spencer, Jeremy 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

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Abstract

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
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Nutrition and Preventive Medicine Faculty of Medicine and Health Sciences > Research Centres > Lifespan Health Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Depositing User:	David Vauzour
Date Deposited:	17 Jan 2012 13:08
Last Modified:	06 Jun 2024 14:37
URI:	https://ueaeprints.uea.ac.uk/id/eprint/34812
DOI:	10.1002/mnfr.200900197

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