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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.

Authors+Show Affiliations

School of Chemistry, Food and Pharmacy, The University of Reading, Whiteknights, Reading, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

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 -