Carbonyl stress and NMDA receptor activation contribute to methylglyoxal neurotoxicity

de Arriba, Susana Garcia , Krügel, Ute, Regenthal, Ralf, Vissiennon, Zacharie, Verdaguer, Esther, Lewerenz, Anne, Garcia-Jorda, Elvira, Pallas, Merce, Camins, Antoni, Münch, Gerald, Nieber, Karen, and Allgaier, Clemens (2006) Carbonyl stress and NMDA receptor activation contribute to methylglyoxal neurotoxicity. Free Radical Biology and Medicine, 40 (5). pp. 779-790.

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Abstract

Methylglyoxal (MG) is a reactive α-ketoaldehyde physiologically generated as a by-product of glycolysis. MG that is able to form protein adducts resulting in advanced glycation end products accumulates under conditions associated with neurodegeneration such as impaired glucose metabolism or oxidative stress. In the present study, short-term exposure of human neuroblastoma SH-SY5Y cells to MG was associated with an early depolarization of the plasma membrane, glutamate release, and formation of reactive oxygen species. In addition, long-term exposure (24 h) of SH-SY5Y cells to MG caused a decrease in cell viability, intracellular ATP, and rhodamine 123 (Rh-123) fluorescence. ATP depletion and the decrease in Rh-123 fluorescence were prevented by carbonyl scavengers, the nitric oxide synthase inhibitor L-NAME, and N-methyl-d-aspartate (NMDA) receptor antagonists. Furthermore, the MG-induced glutamate release and the loss in cell viability were prevented by NMDA receptor antagonists. Therefore, MG renders cells more vulnerable to excitotoxicity. In conclusion, carbonyl scavengers as well as NMDA receptor antagonists may represent effective therapeutic tools to reduce the risk of pathophysiological changes associated with carbonyl stress in neurodegenerative diseases.

Item ID: 3510
Item Type: Article (Refereed Research - C1)
Keywords: methylglyoxal; carbonyl stress; mitochondria; free radicals; neurodegeneration; NMDA receptors;
ISSN: 1873-4596
Date Deposited: 06 Jul 2009 03:35
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1109 Neurosciences @ 75%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology @ 25%
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