Volume 7 Supplement 1
Preventive effect of Curcumin on AD through increasing PS1/E-cadherin/beta-catenin complex mediated by E-cadherin
© Zhang et al; licensee BioMed Central Ltd. 2012
Published: 7 February 2012
The deprivation or abnormality of the molecular function of Wnt/β-catenin triggers the genesis and development of AD, and β-catenin is an important positive mediator in the Wnt/β-catenin signaling pathway. In our previous study, we found that Curcumin could inhibit the expression of β-catenin and prevent AD, but the mechanisms were not fully understood. E-cadherin is a negative mediator in the Wnt/β-catenin signaling pathway, and interacts with β-catenin and PS1 form a trimeric complex, so, we hypothesized that Curcumin prevented AD through increasing PS1/E-cadherin/β-catenin complex by overexpression of E-cadherin.
Plasmid APPswe and BACE1-mychis were transiently co-transfected into SHSY5Y cells by LiposfectaminTM2000. 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 for detecting the effect of Curcumin on the expression of E-cadherin, β-catenin and PS1. And immunofluorescent staining was carried out for detecting the effect of Curcumin on the expression of PS1/E-cadherin/β-catenin complex. ELISA was carried out to detect the generation of Aβ.
ELISA results showed that Curcumin reduced markedly the production of Aβ40/42. RT-PCR and Western blot results showed that the expression of PS1 and β-catenin at mRNA and protein levels were significantly decreased in the transfected cells treated after treatment; however, the protein expression of E-cadherin was increased (P <0.05). Furthermore, all the changes were in a dose and time-dependent manner (P <0.05). Immunofluorescent staining results not only confirmed the above changes, but also showed that the PS1/E-cadherin/β-catenin complex was increased.
Curcumin exerts its preventive effects on AD through increasing PS1/E-cadherin/β-catenin complex by overexpression of E-cadherin.
This work was supported by the National Science Foundation of China (NSFC: 30600196), by the Science Foundation of Chongqing (CSTC: 2006BB5042), and by Projects for Returnee of Ministry of Education (2007–2008).
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.