ABSTRACT
To investigate the effects of emodin on learning and memory and protein kinase C (PKC) signaling pathway in Alzheimer's disease (AD) model mice. 60 APP/PS1 double transgenic AD mice were selected as model mice at the age of 7-8 months, 36 healthy male C57BL/6 mice served as the control group. Morris water maze method and passive avoidance experiment were used to evaluate the memory ability of mice. The thiazole blue (MTT) method and the lactate dehydrogenase (LDH) cytotoxicity test kit were used to evaluate the effect of emodin on the cell viability of hippocampal neurons in HT22 mice treated with ß-amyloid peptide 1-42 (Aß1-42). The effect of emodin on PKC levels was explored using the modified Takai method and Western blotting. Behavioral test results showed that the escape latency of the mice in the model group was longer than that in the control group (P<0.05), and the escape latency was significantly shortened given a emodin prognosis. The MTT and LDH test results showed that emodin to Aß- overexpression induced the protective effect of hippocampus cells in HT22 mice. Western blot analysis showed that the phosphorylation level of PKC in mice increased significantly after emodin administration. Emodin can attenuate oxidative stress and inflammatory response in Alzheimer's model mice by activating PKC pathway, thereby improving cognitive function.
Subject(s)
Alzheimer Disease/metabolism , Drugs, Chinese Herbal/pharmacology , Emodin/pharmacology , Protective Agents/pharmacology , Protein Kinase C/metabolism , Signal Transduction/drug effects , Alzheimer Disease/drug therapy , Amyloid beta-Peptides/pharmacology , Animals , Behavior, Animal/drug effects , Cell Survival/drug effects , Cognition/drug effects , Disease Models, Animal , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/therapeutic use , Emodin/administration & dosage , Emodin/therapeutic use , Hippocampus/pathology , Inflammation/metabolism , Male , Memory/drug effects , Mice , Mice, Inbred C57BL , Mice, Transgenic , Oxidative Stress/drug effects , Peptide Fragments/pharmacology , Phosphorylation/drug effects , Protective Agents/administration & dosage , Protective Agents/therapeutic useABSTRACT
Accumulating evidence has documented that ataxia-telangiectasia group D complementing gene (ATDC) is aberrantly expressed in various cancers and is associated with cancer development and progression. However, little is known about the role of ATDC in glioma tumorigenesis. In this study, we aimed to explore the biological function and regulatory mechanism of ATDC in glioma. We found that ATDC expression was highly upregulated in glioma cell lines. Knockdown of ATDC significantly inhibited the growth and invasion of glioma cells. In contrast, overexpression of ATDC markedly promoted the growth and invasion of glioma cells. Moreover, our results showed that inhibition of ATDC reduced the expression levels of Dishevelled 2 (Dvl2) and ß-catenin and impeded the activation of Wnt/ß-catenin signaling, whereas overexpression of ATDC showed the opposite effect. Knockdown of Dvl2 significantly blocked the promotion effect of ATDC overexpression on activation of Wnt/ß-catenin signaling. In addition, silencing of ß-catenin partially reversed the oncogenic effect of ATDC overexpression in glioma cells. Taken together, out study reveals an oncogenic role of ATDC that drives the growth and invasion of glioma by modulating the Wnt/Dvl2/ß-catenin signaling pathway, suggesting a potential therapeutic target for treatment of glioma.
