Curcumin activates Wnt/β-catenin signaling pathway through inhibiting the activity of GSK-3β in APPswe transfected SY5Y cells

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• 作者：Xiong Zhang^a ; ^b ; Wen-ke Yin^a ; ^b ; ^c ; Xiao-dong Shi^a ; ^b ; ^c ; Yu Li^a ; ^b ; ^c ; ^{liyu100@163.com}
• 关键词：Alzheimer's disease ; Curcumin ; GSK-3&#x3b2 ; &#x3b2 ; -Catenin ; A&#x3b2
• 刊名：European Journal of Pharmaceutical Sciences
• 出版年：2011
• 出版时间：18 April 2011
• 年：2011
• 卷：42
• 期：5
• 页码：540-546
• 全文大小：664 K

文摘

Wnt/&#x3b2;-catenin signaling pathway plays an important role in the genesis and development of Alzheimer's disease. The study aims to investigate the effect of Curcumin on the expression of GSK-3&#x3b2;, &#x3b2;-catenin and CyclinD1 in vitro, which are tightly correlated with Wnt/&#x3b2;-catenin signaling pathway, and also to explore the mechanisms, which will provide a novel therapeutic intervention for treatment of Alzheimer's disease. Plasmid APPswe and BACE1-mychis were transiently co-transfected into SHSY5Y cells by Liposfectamin™2000. The cells were treated with Curcumin at 0, 1.25, 5.0, 20.0 μmol/L for 24 h, or with Curcumin at 5.0 μmol/L for 0, and 12, 24 and 48 h for time course assay. Cell lysates were collected for RT-PCR, Western blot assay and immunofluorescent staining were carried out for detecting the effect of Curcumin on the expression of GSK-3&#x3b2;, &#x3b2;-catenin and CyclinD1. RT-PCR and Western blot results showed that the expression of GSK-3&#x3b2; mRNA and protein significantly decreased in the transfected cells treated with Curcumin, and that the changes were in a dose and time-dependent manner (P < 0.05); however, the protein expression of GSK-3&#x3b2;-Ser9 was increased (P < 0.05). Meanwhile, the expressions of &#x3b2;-catenin and transcriptional factors CyclinD1 mRNA and protein increased and the changes were also in a dose and time-dependent manner (P < 0.05). Immunofluorescent staining results not only confirmed the above changes, but also showed that &#x3b2;-catenin had translocated into the nucleus gradually with the increased dosage of Curcumin. Therefore, GSK-3&#x3b2; is a potential target for treatment of AD. Curcumin could activate the Wnt/&#x3b2;-catenin signaling pathway through inhibiting the expression of GSK-3&#x3b2; and inducing the expression of &#x3b2;-catenin and CyclinD1, which will provide a new theory for treatment of neurodegenerative diseases by Curcumin.