Advanced glycation end products (AGEs) are found in various intraneuronal protein deposits such as neurofibrillary tangles in Alzheimer’s disease and Lewy bodies in Parkinson’s disease. Among AGE precursors, methylglyoxal (MG) is most likely to contribute to intracellular AGE formation, since it is extremely reactive and constantly produced by degradation of triosephosphates. MG accumulation often occurs under hyperglycemic conditions, impaired glucose metabolism and oxidative stress. MG is efficiently metabolized by the cytosolic glyoxalase system that is composed of two enzymes, glyoxalase (GLO) 1 and GLO2, and a catalytic amount of GSH. Isothiocyanates are metabolites derived from the hydrolysis of glucosinolates, a class of compounds present in Brassica vegetables. In particular, sulforaphane (SF), an isothiocyanate produced from glucoraphanin by the enzyme myrosinase, is known for its chemopreventive, anti-inflammatory, cardioprotective and neuroprotective actions. This study was designed to investigate the potential protective effects of SF on MG induced damage in SH-SY5Y neuroblastoma cells. MG caused neuronal cell death as measured by MTT cell viability assay and LDH release and induced apoptosis via activation of caspase 3 and modulating signaling kinases involved in survival and cell death. MG significantly increased intracellular ROS production and decreased GSH levels and glucose uptake. SF treatment significantly counteracted cell death and apoptosis induced by MG and partially inhibited MG negative modulation of signaling kinases. SF treatment reduced MG induced oxidative stress decreasing intracellular ROS production and increasing GSH levels. Moreover, SF was able to increase glucose uptake in MG treated cells and significantly increased GLO1 protein expression and activity, eliciting a fundamental role in MG detoxification.
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|Titolo:||Sulforaphane pleiotropic effects in counteracting carbonyl stress in SH-SY5Y cells|
|Data di pubblicazione:||2013|
|Appare nelle tipologie:||Abstract atto convegno su volume|