title: Evidence that glycine induces lipid peroxidation and decreases glutathione concentrations in rat cerebellum.
abstract: Patients with non-ketotic hyperglycinemia (NKH) present severe neurological symptoms and brain abnormalities involving cerebellum. Although the pathomechanisms underlying the cerebellum damage have not been studied, high tissue levels of glycine (GLY), the biochemical hallmark of this disorder have been suggested to contribute to the neuropathology of this disease. We investigated the in vitro effects of GLY on important parameters of oxidative stress and energy metabolism in cerebellum of 30-day-old rats. Our results show that GLY increased 2',7'-dichlorofluorescin oxidation, suggesting that reactive species production are augmented by GLY in the cerebellum. However, hydrogen peroxide generation was not altered by GLY. GLY also increased thiobarbituric acid-reactive substances (TBA-RS) levels and reduced the glutathione (GSH) content, indicating that this amino acid provokes lipid oxidative damage and compromises the non-enzymatic antioxidant defenses, respectively, in cerebellum. The antioxidants melatonin and trolox (the hydrosoluble analog of vitamin E) prevented the GLY-induced increase of TBA-RS and decrease of GSH in cerebellum, indicating the involvement of hydroxyl and peroxyl radicals in these effects. The NMDA receptor antagonist MK-801 also attenuated GLY-induced decrease of GSH, suggesting that this effect is mediated through NMDA receptor. In contrast, GLY did not alter the protein carbonyl formation and total and protein-bound sulfhydryl group content, as well as catalase and superoxide dismutase activities. Furthermore, GLY did not alter the activities of the respiratory chain complexes and creatine kinase. Our present data indicate that oxidative stress elicited by GLY in vitro may be a potential pathomechanism involved in the cerebellar dysfunction observed in NKH.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal de Rio Grande do Sul, Rua Ramiro Barcelos N° 2600 - Attached, Porto Alegre, RS, CEP 90035-003, Brazil.
authors.forename: Alana Pimentel
authors.initials: AP
authors.lastname: Moura
authors.forename: Mateus
authors.initials: M
authors.lastname: Grings
authors.forename: Gustavo Flora
authors.initials: GF
authors.lastname: Marcowich
authors.forename: Anna Paula
authors.initials: AP
authors.lastname: Bumbel
authors.forename: Belisa
authors.initials: B
authors.lastname: Parmeggiani
authors.forename: Leonardo
authors.initials: L
authors.lastname: de Moura Alvorcem
authors.forename: Moacir
authors.initials: M
authors.lastname: Wajner
authors.forename: Guilhian
authors.initials: G
authors.lastname: Leipnitz
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D005978:Glutathione / Q000378:metabolism*; D005998:Glycine / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D016194:Receptors, N-Methyl-D-Aspartate; D006861:Hydrogen Peroxide; D005978:Glutathione; D005998:Glycine