Effect of JGK-263 as a new glycogen synthase kinase-3ß inhibitor on extrinsic apoptosis pathway in motor neuronal cells.
Biochem Biophys Res Commun
; 439(2): 309-14, 2013 Sep 20.
Article
em En
| MEDLINE
| ID: mdl-23899525
ABSTRACT
Glycogen synthase kinase-3ß (GSK-3ß) has been identified as one of the important pathogenic mechanisms in motor neuronal death. GSK-3ß inhibitor has been investigated as a modulator of apoptosis and has been shown to confer significant protective effects on cell death in neurodegenerative diseases. However, GSK-3ß is known to have paradoxical effects on apoptosis subtypes, i.e., pro-apoptotic in mitochondrial-associated intrinsic apoptosis, but anti-apoptotic in death receptor-related extrinsic apoptosis. In this study, we evaluated the effect of a new GSK-3ß inhibitor (JGK-263) on motor neuron cell survival and apoptosis, by using low to high doses of JGK-263 after 48 h of serum withdrawal, and monitoring changes in extrinsic apoptosis pathway components, including Fas, FasL, cleaved caspase-8, p38α, and the Fas-Daxx interaction. Cell survival peaked after treatment of serum-deprived cells with 50 µM JGK-263. The present study showed that treatment with JGK-263 reduced serum-deprivation-induced motor neuronal apoptosis by inactivating not only the intrinsic, but also the extrinsic apoptosis pathway. These results suggest that JGK-263 has a neuroprotective effect through effective modulation of the extrinsic apoptosis pathway in motor neuron degeneration.
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Base de dados:
MEDLINE
Assunto principal:
Apoptose
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Quinase 3 da Glicogênio Sintase
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Inibidores de Proteínas Quinases
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Neurônios Motores
Limite:
Animals
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article