HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

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.

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.
AuthorsDavid Vauzour, Maria Buonfiglio, Giulia Corona, Joselita Chirafisi, Katerina Vafeiadou, Cristina Angeloni, Silvana Hrelia, Patrizia Hrelia, Jeremy P E Spencer
JournalMolecular nutrition & food research (Mol Nutr Food Res) Vol. 54 Issue 4 Pg. 532-42 (Apr 2010) ISSN: 1613-4133 [Electronic] Germany
PMID20166144 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Isothiocyanates
  • NF-E2-Related Factor 2
  • Neuroprotective Agents
  • Sulfoxides
  • Thiocyanates
  • 5-S-cysteaminyldopamine
  • NAD(P)H Dehydrogenase (Quinone)
  • Nqo1 protein, mouse
  • Glutathione Reductase
  • Thioredoxin-Disulfide Reductase
  • Glutathione Transferase
  • Extracellular Signal-Regulated MAP Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • sulforaphane
  • Glutathione
  • Dopamine
Topics
  • 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)
  • Isothiocyanates
  • 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)
  • Sulfoxides
  • Thiocyanates (pharmacology)
  • Thioredoxin-Disulfide Reductase (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: