title: Carbonyl stress and NMDA receptor activation contribute to methylglyoxal neurotoxicity.
abstract: Methylglyoxal (MG) is a reactive alpha-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.
authors.affiliation: Rudolf-Boehm Institute Pharmacology and Toxicology, University of Leipzig, Germany.
authors.forename: Susana Garcia
authors.initials: SG
authors.lastname: de Arriba
authors.forename: Ute
authors.initials: U
authors.lastname: Krügel
authors.forename: Ralf
authors.initials: R
authors.lastname: Regenthal
authors.forename: Zacharie
authors.initials: Z
authors.lastname: Vissiennon
authors.forename: Esther
authors.initials: E
authors.lastname: Verdaguer
authors.forename: Anne
authors.initials: A
authors.lastname: Lewerenz
authors.forename: Elvira
authors.initials: E
authors.lastname: García-Jordá
authors.forename: Mercé
authors.initials: M
authors.lastname: Pallas
authors.forename: Antoni
authors.initials: A
authors.lastname: Camins
authors.forename: Gerald
authors.initials: G
authors.lastname: Münch
authors.forename: Karen
authors.initials: K
authors.lastname: Nieber
authors.forename: Clemens
authors.initials: C
authors.lastname: Allgaier
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D001692:Biological Transport; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D011765:Pyruvaldehyde / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists* / Q000235:genetics; D020112:Rhodamine 123 / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D016194:Receptors, N-Methyl-D-Aspartate; D020112:Rhodamine 123; D018698:Glutamic Acid; D011765:Pyruvaldehyde; D000255:Adenosine Triphosphate