Effects of high copper on Wnt/β-catenin signaling pathway in hepatocytes
10.3969/j.issn.1002-0152.2017.11.002
- VernacularTitle:高铜对于肝细胞Wnt/β-catenin信号通路的影响
- Author:
Yanan HUANG
1
,
2
;
Hai LI
;
Jianjian DONG
;
Nan CHENG
;
Yongzhu HAN
Author Information
1. 安徽中医药大学研究生部 合肥230038
2. 安徽中医药大学神经病学研究所附属医院神经内科
- Keywords:
Wilson disease;
Wnt/β-catenin signaling pathway;
High copper;
Oxidative stress;
Hepatocyte injury
- From:
Chinese Journal of Nervous and Mental Diseases
2017;43(11):646-650
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the effect of high copper on Wnt /β-catenin signaling pathway and oxidative stress. Methods BRL-3A cells were incubated with different concentrations of CuSO4.The cell growth and proliferation wre assessed using MRR method.The production of reactive oxygen species(ROS)and mitochondrial membrane potential (JC-1) were examined usingf flow cytometry. The content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) were detected by microplate reader. The expression of protein was detected by Western Blot. Results①The results of MTT showed that CuSO4inhibited the growth and proliferation of BRL-3A cells in a time- and concentration-dependent manner(P<0.01).②Flow cytometry results showed that CuSO4induced a large amount of ROS and significantly decreased the fluorescence intensity of JC-1 in BRL-3A cells (P<0.01). ③ Microplate reader results showed that CuSO4increased the content of MDA and decreased the activity of SOD (P<0.05).④Western blotting assay showed that CuSO4significantly decreased the total expression levels of β-catenin and p-Ser 9-GSK-3β protein as well as nuclear levels of p-(S33+S37)-β-catenin and c-Myc (P<0.01) and increased expression levels of GSK-3β、DKK1、Dishevelled3 protein in BRL-3A cells. Conclusion High copper can induce oxidative stress and induce Wnt /β-catenin signaling pathway to deactivate liver cells,leading to hepatocellular injury.
