title: Nitric oxide mediates glutamate-induced mitochondrial depolarization in rat cortical neurons.
abstract: Mitochondria have been considered to be a target for glutamate neurotoxicity. The aim of the present work was to investigate the mechanisms leading to glutamate-mediated mitochondrial deenergization, as measured by mitochondrial membrane potential and cell respiration in cultured neurons. Glutamate exposure to cells induced pronounced mitochondrial depolarization associated with an impairment in neuronal respiration, leading to neuronal ATP depletion. These effects were prevented by both the nitric oxide (. NO) synthase inhibitor Nomega-nitro-l-arginine methyl ester and by the N-methyl-d-aspartate glutamate-subtype receptor inhibitor d-(-)-2-amino-5-phosphopentanoate. Our results suggest that glutamate causes ATP depletion by collapsing mitochondrial membrane potential through a.NO-mediated mechanism.
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Salamanca, Edificio Departamental, Avda. del Campo Charro, 37007, Salamanca, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Almeida
authors.forename: J P
authors.initials: JP
authors.lastname: Bolaños
authors.forename: J M
authors.initials: JM
authors.lastname: Medina
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018698:Glutamic Acid / Q000633:toxicity*; D016014:Linear Models; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000648:ultrastructure; D009498:Neurotoxins / Q000633:toxicity*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004791:Enzyme Inhibitors; D009498:Neurotoxins; D009569:Nitric Oxide; D018698:Glutamic Acid; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester