Neuroprotective effect of sulforaphane against methylglyoxal cytotoxicity.

Abstract

Glycation, an endogenous process that leads to the production of advanced glycation end products (AGEs), plays a role in the etiopathogenesis of different neurodegenerative diseases, such as Alzheimer's disease (AD). Methylglyoxal is the most potent precursor of AGEs, and high levels of methylglyoxal have been found in the cerebrospinal fluid of AD patients. Methylglyoxal may contribute to AD both inducing extensive protein cross-linking and mediating oxidative stress. The aim of this study was to investigate the role of sulforaphane, an isothiocyanate found in cruciferous vegetables, in counteracting methylglyoxal-induced damage in SH-SY5Y neuroblastoma cells. The data demonstrated that sulforaphane protects cells against glycative damage by inhibiting activation of the caspase-3 enzyme, reducing the phosphorylation of MAPK signaling pathways (ERK1/2, JNK, and p38), reducing oxidative stress, and increasing intracellular glutathione levels. For the first time, we demonstrate that sulforaphane enhances the methylglyoxal detoxifying system, increasing the expression and activity of glyoxalase 1. Sulforaphane modulated brain-derived neurotrophic factor and its pathway, whose dysregulation is related to AD development. Moreover, sulforaphane was able to revert the reduction of glucose uptake caused by methylglyoxal. In conclusion, sulforaphane demonstrates pleiotropic behavior thanks to its ability to act on different cellular targets, suggesting a potential role in preventing/counteracting multifactorial neurodegenerative diseases such as Alzheimer's.

• Authors: Cristina Angeloni, Marco Malaguti, Benedetta Rizzo, Maria Cristina Barbalace, Daniele Fabbri, Silvana Hrelia
• Journal: Chemical research in toxicology (Chem Res Toxicol) Vol. 28 Issue 6 Pg. 1234-45 (Jun 15 2015) ISSN: 1520-5010 [Electronic] United States
• PMID: 25933243 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Isothiocyanates
• Neuroprotective Agents
• Sulfoxides
• Pyruvaldehyde
• sulforaphane
• Glucose

Topics

• Apoptosis (drug effects)
• Dose-Response Relationship, Drug
• Glucose (metabolism)
• Humans
• Isothiocyanates (pharmacology)
• Neuroprotective Agents (pharmacology)
• Oxidative Stress (drug effects)
• Pyruvaldehyde (toxicity)
• Structure-Activity Relationship
• Sulfoxides
• Tumor Cells, Cultured