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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.
Mol Nutr Food Res. 2010 Apr; 54(4):532-42.MN

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.

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Authors+Show Affiliations

Vauzour D
School of Chemistry, Food and Pharmacy, The University of Reading, Whiteknights, Reading, UK.
Buonfiglio M
No affiliation info available
Corona G
No affiliation info available
Chirafisi J
No affiliation info available
Vafeiadou K
No affiliation info available
Angeloni C
No affiliation info available
Hrelia S
No affiliation info available
Hrelia P
No affiliation info available
Spencer JP
No affiliation info available

MeSH

AnimalsCell DeathCells, CulturedCerebral CortexDopamineEnzyme ActivationExtracellular Signal-Regulated MAP KinasesGlutathioneGlutathione ReductaseGlutathione TransferaseIsothiocyanatesMiceMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3NAD(P)H Dehydrogenase (Quinone)NF-E2-Related Factor 2NeuronsNeuroprotective AgentsPhosphorylationThiocyanatesThioredoxin-Disulfide Reductase

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20166144

Citation

Vauzour, David, et al. "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, vol. 54, no. 4, 2010, pp. 532-42.
Vauzour D, Buonfiglio M, Corona G, et al. 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. Mol Nutr Food Res. 2010;54(4):532-42.
Vauzour, D., Buonfiglio, M., Corona, G., Chirafisi, J., Vafeiadou, K., Angeloni, C., Hrelia, S., Hrelia, P., & Spencer, J. P. (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), 532-42. https://doi.org/10.1002/mnfr.200900197
Vauzour D, et al. 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. Mol Nutr Food Res. 2010;54(4):532-42. PubMed PMID: 20166144.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Vauzour,David, AU - Buonfiglio,Maria, AU - Corona,Giulia, AU - Chirafisi,Joselita, AU - Vafeiadou,Katerina, AU - Angeloni,Cristina, AU - Hrelia,Silvana, AU - Hrelia,Patrizia, AU - Spencer,Jeremy P E, PY - 2010/2/19/entrez PY - 2010/2/19/pubmed PY - 2010/7/2/medline SP - 532 EP - 42 JF - Molecular nutrition & food research JO - Mol Nutr Food Res VL - 54 IS - 4 N2 - 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. SN - 1613-4133 UR - https://www.unboundmedicine.com/medline/citation/20166144/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_ L2 - https://doi.org/10.1002/mnfr.200900197 DB - PRIME DP - Unbound Medicine ER -