Carbonyl stress and NMDA receptor activation contribute to methylglyoxal neurotoxicity

Methylglyoxal Activates Nociceptors through Transient Receptor Potential Channel A1 (TRPA1)

“…Other effects of MG leading to increased excitability are not ruled out and have been described earlier. For example, 300 M MG induced a slowly developing depolarization in cortical neurons (75), whereas a fast depolarization was observed by 1 mM MG in isolated rat pancreatic islet cells (76). However, in human skin, MG is plainly a noxious and irritant compound; intradermal injections caused burning pain for a few minutes and a typical axon reflex flare response indicative of peptidergic nociceptor activation (10 mM; 15 l).…”

Methylglyoxal and carboxyethyllysine reduce glutamate uptake and S100B secretion in the hippocampus independently of RAGE activation

“…b S100B secretion-*significantly different from control and AG (0.25, 0.5 and 1 mM) Volterra and Meldolesi 2005;Nardin et al 2009;Quincozes-Santos et al 2014;Takano et al 2014). Furthermore, studies that have evaluated the methylglyoxal-induced changes in cultures of neurons or neuroblastoma have shown that these cells have a high susceptibility to damage caused by MG (De Arriba et al 2006;Di Loreto et al 2008). In contrast, astrocytes, which play a key role in neuronal cell survival and brain homeostasis, are more resistant to MG-induced impairment, in part because they present higher expression and activity of the glyoxalase system compared to neurons (Bélanger et al 2011).…”

“…Unchanged levels of astrocyte glutamate transporters studied in STZinduced diabetic rats have been reported (Coleman et al 2004), while others have related the involvement of NMDA (N-methyl-d-aspartate) receptor activation following MG treatment (De Arriba et al 2006), indicating that alterations in glutamatergic transmission and excitotoxicity observed in diabetic rats could involve changes in the affinity and expression of glutamate receptors (Gardoni et al 2002). Our findings suggest that the impairment of glutamate uptake, which in turn could increase glutamate levels in the synaptic cleft, generates glutamatergic dysfunction.…”

Dihydromyricetin ameliorates the oxidative stress response induced by methylglyoxal via the AMPK/GLUT4 signaling pathway in PC12 cells

“…Twenty-four hours later, AGTE, TAPE, TAEA, TABU, TAW, MG or DMY was applied. The doses of DMY and MG were selected based on previous studies (de Arriba et al, 2006Arriba et al, , 2007Xia et al, 2014;Zhao et al, 2014). At end of the treatments, MTT (5 mg/mL in phosphate-buffered saline, PBS) was added to each well, and the plates were incubated for 4 h at 37 • C. Formazan dissolved in dimethyl sulfoxide (DMSO) was added to the wells, and the plates were agitated for 10-20 min on a shaker.…”