GMI ganglioside prevents seizures, Na+,K+-ATPase activity inhibition and oxidative stress induced by glutaric acid and pentylenetetrazole

GMI ganglioside prevents seizures, Na+,K+-ATPase activity inhibition and oxidative stress induced by glutaric acid and pentylenetetrazole

Autor Fighera, M. R. Google Scholar
Royes, LFF Google Scholar
Furian, A. F. Google Scholar
Oliveira, M. S. Google Scholar
Fiorenza, N. G. Google Scholar
Frussa, R. Google Scholar
Petry, J. C. Google Scholar
Coelho, R. C. Google Scholar
Mello, C. F. Google Scholar
Instituição Universidade Federal de Sergipe (UFS)
Universidade Federal de São Paulo (UNIFESP)
Resumo Monosialoganglioside (GM1) is a glycosphingolipid that protects against some neurological conditions, such as seizures and ischemia. Glutaric acidemia type I (GA-I) is an inherited disease characterized by striatal degeneration, seizures, and accumulation of glutaric acid (GA). in this study, we show that GA inhibits Na+,K+-ATPase activity and increases oxidative damage markers (total protein carbonylation and thiobarbituric acid-reactive substances-TBARS) production in striatal homogenates from rats in vitro and ex vivo. It is also shown that GM1 (50 mg/kg, i.p., twice) protects against GA-induced (4 mu mol/striatum) seizures, protein carbonylation, TBARS increase, and inhibition of Na+,K+-ATI`ase activity ex vivo. Convulsive episodes induced by GA strongly correlated with Na+,K+-ATPase activity inhibition in the injected striatum but not with oxidative stress marker measures. Muscimol (46 pmol/striatum), but not MK-801 (3 nmol/ striatum) and DNQX (8 nmol/striatum) prevented GA-induced convulsions, increase of TBARS and protein carbonylation and inhibition of Na+,K+-ATPase activity. the protection of GM1 and muscimol against GA-induced seizures strongly correlated with Na+,K+-ATPase activity maintenance ex vivo. in addition, GM1 (50-200 mu M) protected against Na+K+-ATPase inhibition induced by GA (6 mM) but not against oxidative damage in vitro. GM1 also decreased pentylenetetrazole (PTZ)-induced (1.8 mu mol/striatum) seizures, Na+,K+-ATPase inhibition, and increase of TBARS and protein carbonyl in the striatum. These data suggest that Na+,K+-ATPase and GABA(A) receptor-mediated mechanisms may play important roles in GA-induced seizures and in their prevention by GM1. (c) 2006 Elsevier Inc. All rights reserved.
Palavra-chave seizure
glutaric acid
oxidative damage
protein carbonylation
Na+,K+-ATPase activity
Idioma Inglês
Data de publicação 2006-06-01
Publicado em Neurobiology of Disease. San Diego: Academic Press Inc Elsevier Science, v. 22, n. 3, p. 611-623, 2006.
ISSN 0969-9961 (Sherpa/Romeo, fator de impacto)
Publicador Elsevier B.V.
Extensão 611-623
Direito de acesso Acesso restrito
Tipo Artigo
Web of Science WOS:000238462600016
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