Wang Yun-Liang, Ju Bo, Zhang Yu-Zhen, Yin Hong-Lei, Liu Ya-Jun, Wang Shan-Shan, Zeng Zhi-Lei, Yang Xiao-Peng, Wang Hai-Tao, Li Jin-Feng
Department of Neurology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Neurology, The 148th Hospital of PLA, Zibo, China.
Cell Physiol Biochem. 2017;43(6):2226-2241. doi: 10.1159/000484302. Epub 2017 Oct 25.
BACKGROUND/AIMS: The study aimed to investigate the protective effect of curcumin against oxidative stress-induced injury of Parkinson's disease (PD) through the Wnt/β-catenin signaling pathway in rats.
The successfully established PD rat models and normal healthy rats were randomly assigned into the 6-hydroxydopamine (6-OHDA), the curcumin (Cur) and the control groups. Immunohistochemistry was used to detect the positive expression of tyrosine hydroxylase (TH), dopamine transporter (DAT) and glial fibrillary acidic protein (GFAP). Deutocerebrum primary cells were extracted and classified into the control, 6-OHDA, Cur (5, 10, 15 µmol/L), Dickkopf-1 (DKK-1) and Cur + DKK-1 groups. MTT assays, adhesion tests and TUNEL staining were used to assess cell viability, adhesion and apoptosis, respectively. Western blotting and qRT-PCR were used to examine the protein and mRNA expressions of Wnt3a and β-catenin and the c-myc and cyclinD1 mRNA expressions.
TH and DAT expressions in the Cur group were elevated and GFAP was reduced compared with the 6-OHDA group. Curcumin enhanced viability, survival and adhesion and attenuated apoptosis of deutocerebrum primary cells by activating the Wnt/β-catenin signaling pathway. Higher Wnt3a and β-catenin mRNA and protein expressions and c-myc and cyclinD1 mRNA expressions, enhanced superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) contents, decreased malondialdehyde (MDA) content and elevated mitochondrial membrane potential (∆ψm) were found in the 10 and 15 µmol/L Cur groups compared with the 6-OHDA group. However, opposite tendencies were found in the Cur + DKK-1 group compared to the 10 µmol/L Cur group.
This study suggests that curcumin could protect against oxidative stress-induced injury in PD rats via the Wnt/β-catenin signaling pathway.
背景/目的:本研究旨在探讨姜黄素通过Wnt/β-连环蛋白信号通路对帕金森病(PD)大鼠氧化应激诱导损伤的保护作用。
将成功建立的PD大鼠模型和正常健康大鼠随机分为6-羟基多巴胺(6-OHDA)组、姜黄素(Cur)组和对照组。采用免疫组织化学法检测酪氨酸羟化酶(TH)、多巴胺转运体(DAT)和胶质纤维酸性蛋白(GFAP)的阳性表达。提取中脑原代细胞,分为对照组、6-OHDA组、Cur(5、10、15 μmol/L)组、Dickkopf-1(DKK-1)组和Cur+DKK-1组。分别采用MTT法、黏附试验和TUNEL染色评估细胞活力、黏附及凋亡情况。采用蛋白质印迹法和qRT-PCR检测Wnt3a和β-连环蛋白的蛋白及mRNA表达以及c-myc和cyclinD1 mRNA表达。
与6-OHDA组相比,Cur组TH和DAT表达升高,GFAP表达降低。姜黄素通过激活Wnt/β-连环蛋白信号通路增强中脑原代细胞的活力、存活率和黏附能力,并减轻细胞凋亡。与6-OHDA组相比,10和15 μmol/L Cur组Wnt3a和β-连环蛋白的mRNA及蛋白表达、c-myc和cyclinD1 mRNA表达升高,超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)含量增加,丙二醛(MDA)含量降低,线粒体膜电位(∆ψm)升高。然而,与10 μmol/L Cur组相比,Cur+DKK-1组出现相反趋势。
本研究表明,姜黄素可通过Wnt/β-连环蛋白信号通路保护PD大鼠免受氧化应激诱导的损伤。