A Bcl-2 antisense oligonucleotide increases alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) toxicity in cortical cultures.
Ann Neurol
; 42(4): 580-7, 1997 Oct.
Article
em En
| MEDLINE
| ID: mdl-9382469
ABSTRACT
Both alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor-mediated neurotoxicity and the induction of death-regulatory genes have been implicated in the pathophysiology of delayed ischemic neuronal injury. To assess the role of the antiapoptotic gene Bcl-2 in the modulation of AMPA toxicity, we exposed neuron-enriched cultures from rat cerebral cortex to AMPA, in the absence or presence of an antisense oligodeoxynucleotide (ODN) directed against Bcl-2. AMPA produced concentration-dependent toxicity detected by a decrease in fluorescence of the redox indicator Alamar blue and by an increase in lactic acid dehydrogenase release. This effect was accompanied by the induction of Bcl-2 protein expression, with maximal induction at 100 microM AMPA. A phosphorothioate antisense ODN against Bcl-2 reduced the AMPA-stimulated induction of Bcl-2 protein levels, detected by western blotting, by about 70%. In the presence of the antisense ODN, but not sense or scrambled ODNs, the toxicity of 100 microM AMPA was increased by about 60%. These findings suggest that induction of Bcl-2 expression by AMPA may have a protective role to limit AMPA receptor-mediated neuronal damage and that modifying Bcl-2 expression could have therapeutic potential in ischemia.
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Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico
/
Agonistas de Aminoácidos Excitatórios
/
Proteínas Proto-Oncogênicas c-bcl-2
/
Neurônios
Limite:
Animals
Idioma:
En
Revista:
Ann Neurol
Ano de publicação:
1997
Tipo de documento:
Article
País de afiliação:
Estados Unidos