Activation of muscarinic receptors inhibits glutamate-induced GSK-3β overactivation in PC12 cells

作者：Ma, Ke; Yang, Li-min; Chen, Hong-zhuan; Lu, Yang^*

来源：Acta Pharmacologica Sinica, 2013, 34(7): 886-892.

DOI：10.1038/aps.2013.42

• muscarinic receptors
• carbachol
• neuroprotection
• glutamate
• excitotoxicity
• GSK-3 beta
• b-catenin
• PC12 cell
• Alzheimer's disease

Aim: To investigate the actions of the muscarinic agonist carbachol on glutamate-induced neurotoxicity in PC12 cells, and the underlying mechanisms. @@@ Methods: PC12 cells were treated with different concentrations of glutamate for 24 or 48 h. The cell viability was measured using MTT assay, and the expression and activation of GSK-3 beta were detected with Western blot. beta-Catenin translocation was detected using immunofluorescence. Luciferase reporter assay and real-time PCR were used to analyze the transcriptional activity of beta-catenin. @@@ Results: Glutamate (1, 3, and 10 mmol/L) induced PC12 cell death in a dose-dependent manner. Moreover, treatment of the cells with glutamate (1 mmol/L) caused significant overactivation of GSK-3 beta and prevented beta-catenin translocation to the nucleus. Pretreatment with carbachol (0.01 mu mol/L) blocked glutamate-induced cell death and GSK-3 beta overactivation, and markedly enhanced beta-catenin transcriptional activity. @@@ Conclusion: Activation of muscarinic receptors exerts neuroprotection in PC12 cells by attenuating glutamate-induced GSK-3 beta overactivation, suggesting potential benefits of muscarinic agonists for Alzheimer's disease.

• 出版日期2013-7
• 单位上海交通大学