Involvement of Wnt/beta-catenin signaling in tripchlorolide protecting against oligomeric beta-amyloid-(1-42)-induced neuronal apoptosis / 药学学报
Acta Pharmaceutica Sinica
; (12): 853-859, 2010.
Article
em Zh
| WPRIM
| ID: wpr-354564
Biblioteca responsável:
WPRO
ABSTRACT
This study is to explore whether the Wnt/beta-catenin signaling pathway is involved in the process of tripchlorolide (T4) protecting against oligomeric Abeta(1-42)-induced neuronal apoptosis. Primary cultured cortical neurons were used for the experiments on day 6 or 7. The oligomeric Abeta(1-42) (5 micromol x L(-1) for 24 h) was applied to induce neuronal apoptosis. Prior to treatment with Abeta(1-42) for 24 h, the cultured neurons were pre-incubated with T4 (2.5, 10, and 40 nmol x L(-1)), Wnt3a (Wnt signaling agonists) and Dkk1 (inhibitors) for indicated time. Then the cell viability, neuronal apoptosis, and protein levels of Wnt, glycogen synthase kinase 3beta (GSK3beta), beta-catenin and phospho-beta-catenin were measured by MTT assay, TUNEL staining and Western blotting, respectively. The result demonstrated that oligomeric Abeta(1-42) induced apoptotic neuronal cell death in a time- and dose-dependent manner. Pretreatment with T4 significantly increased the neuronal cell survival and attenuated neuronal apoptosis. Moreover, oligomeric Abeta(1-42)-induced phosphorylation of beta-catenin and GSK3beta was markedly inhibited by T4. Additionally, T4 stabilized cytoplasmic beta-catenin. These results indicate that tripchlorolide protects against the neurotoxicity of Abeta by regulating Wnt/beta-catenin signaling pathway. This may provide insight into the clinical application of tripchlorolide to Alzheimer's disease.
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Índice:
WPRIM
Assunto principal:
Fragmentos de Peptídeos
/
Farmacologia
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Fenantrenos
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Fosforilação
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Plantas Medicinais
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Transdução de Sinais
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Sobrevivência Celular
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Células Cultivadas
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Córtex Cerebral
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Química
Limite:
Animals
/
Pregnancy
Idioma:
Zh
Revista:
Acta Pharmaceutica Sinica
Ano de publicação:
2010
Tipo de documento:
Article