Involvement of Wnt/beta-catenin signaling in tripchlorolide protecting against oligomeric beta-amyloid-(1-42)-induced neuronal apoptosis.
- Author:
Ming WU
1
;
Yuan-gui ZHU
;
Xiao-dong PAN
;
Nan LIN
;
Jing ZHANG
;
Xiao-chun CHEN
Author Information
1. Department of Neurology, Union Hospital of Fujian Medical University, China.
- Publication Type:Journal Article
- MeSH:
Amyloid beta-Peptides;
antagonists & inhibitors;
toxicity;
Animals;
Apoptosis;
drug effects;
Cell Survival;
drug effects;
Cells, Cultured;
Cerebral Cortex;
cytology;
Diterpenes;
isolation & purification;
pharmacology;
Female;
Fetus;
Glycogen Synthase Kinase 3;
metabolism;
Glycogen Synthase Kinase 3 beta;
Neurons;
cytology;
drug effects;
Neuroprotective Agents;
isolation & purification;
pharmacology;
Peptide Fragments;
antagonists & inhibitors;
toxicity;
Phenanthrenes;
isolation & purification;
pharmacology;
Phosphorylation;
Plants, Medicinal;
chemistry;
Pregnancy;
Rats;
Rats, Sprague-Dawley;
Signal Transduction;
Tripterygium;
chemistry;
Wnt Proteins;
metabolism;
beta Catenin;
metabolism
- From:
Acta Pharmaceutica Sinica
2010;45(7):853-859
- CountryChina
- Language:Chinese
-
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.
