Diazoxide and cyclosporin A protect primary cholinergic neurons against beta-amyloid (1-42)-induced cytotoxicity.
Neurol Res
; 35(5): 529-36, 2013 Jun.
Article
em En
| MEDLINE
| ID: mdl-23595141
ABSTRACT
OBJECTIVE:
Activation of mitochondrial (MitoKATP) channels was found to protect against anoxic and chemical stress in brain. This present study sought to investigate the ability of diazoxide and cyclosporin A to antagonize cytotoxicity induced by beta-amyloid peptide (A-beta1-42) in cultured rat primary basal forebrain cholinergic neurons.METHODS:
Cytotoxicity was induced by A-beta1-42 (2 µM) in the presence of either diazoxide (500 µM), a selective opener of the mitochondrial ATP-sensitive potassium channel (MitoKATP), or cyclosporin A (20 µM), an inhibitor of the mitochondrial permeability transition pore (MTP), or the combination of both the reagents. We determined cell morphology and cell viability using MTT assay and expression levels of anti-apoptotic protein (Bcl-2), pro-apoptotic proteins (Bax, cytochrome C, caspase-3 and cleaved caspase-3) using Western blotting at 24 hours and 72 hours.RESULTS:
Cell viability decreased markedly after exposure to A-beta1-42 for 72 hours with a decrease in the expression of Bcl-2 protein and cytochrome C and an increase in the caspase-3 and cleaved caspase-3 levels. Both diazoxide and cyclosporin A exerted significant protective effects on cell viability by ameliorating the decrease in Bcl-2 and the increase in cytochrome c and caspase-3 activity induced by A-beta1-42. The combination of both the reagents had a greater protective effect than either one alone.CONCLUSIONS:
The present research demonstrates that activation of MitoKATP channels independently or in combination with inhibitors of the MTP can elicit a protective effect against primary cholinergic neuron cytotoxicity induced by A-beta1-42. These findings suggest new mitochondrial targets for the development of therapeutic agents against A-beta-induced cytotoxicity.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
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Sobrevivência Celular
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Peptídeos beta-Amiloides
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Fármacos Neuroprotetores
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Proteínas Reguladoras de Apoptose
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Neurônios Colinérgicos
Limite:
Animals
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article