Effect of PACS-2 on the development of Alzheimer's disease
10.3969/j.issn.1673-9701.2024.05.003
- VernacularTitle:PACS-2在阿尔茨海默病发展中作用机制研究
- Author:
Yanyun WANG
1
;
Qunying YE
1
;
Jun QIAN
1
;
Zhipeng LIU
1
;
Hongbo LUO
1
;
Yun LI
2
Author Information
1. Department of Neurology, the Fifth Affiliated (Zhuhai) Hospital of Zunyi Medical University, Zhuhai 519000, Guangdong, China
2. Department of Nephrology and Rheumatology, the Fifth Affiliated (Zhuhai) Hospital of Zunyi Medical University, Zhuhai 519000, Guangdong, China
- Publication Type:Journal Article
- Keywords:
Phosphofurin acidic cluster sorting protein-2;
Alzheimer's disease;
N2a/APP695swe cell;
Mitochondrial dysfunction;
Apoptosis
- From:
China Modern Doctor
2024;62(5):11-15
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the involvement of phosphofurin acidic cluster sorting protein-2(PACS-2)in mitochondrial function and apoptosis in N2a/APP695swe cells and further explore the role and significance of PACS-2 in the development of Alzheimer's disease(AD).Methods The CCK8 method was used to analyze the cell survival rate of N2a/APP695swe cells treated with different concentrations of tetrahydroxy stilbene glycoside(TSG)for 48h and to select the appropriate concentration of TSG for subsequent experiments.N2a/WT cells and N2a/APP695swe cells were routinely cultured in vitro,and the experimental cells were divided into 3 groups:blank control group(WT group):N2a/WT cells;model group(APP group):N2a/APP695swe cells;treatment group(TSG group):N2a/APP695swe cells with appropriate concentrations of TSG intervention.TUNEL method to observe apoptosis by fluorescence microscopy;JC-1 method for flow detection of cellular mitochondrial membrane potential;WB to detect protein expression of PACS-2;RT-qPCR to detect PACS-2 mRNA expression.Results CCK8 method was used to analyze the cell survival rate of different concentrations of TSG acting on cells after 48h:the protective effect of 100 μmol/L TSG was the most significant and the difference was statistically significant(P<0.01).The TUNEL method of fluorescence microscopy observed the apoptosis:compared with the WT group,the apoptosis rate of APP group was increased,compared with the APP group,the apoptosis rate of TSG group was decreased,and the differences were statistically significant(P<0.05).The JC-1 method was used to detect the mitochondrial membrane potential of cells:compared with the WT group,the membrane potential of APP group was decreased,compared with the APP group,the membrane potential of TSG group was increased,and the differences were statistically significant(P<0.05);Western blot(WB)detection of PACS-2 protein expression:compared with the WT group,PACS-2 expression was significantly higher in the APP group,and compared with the APP group,PACS-2 expression was significantly lower in the TSG group,with statistically significant differences(P<0.05);The RT-qPCR detected the mRNA expression of PACS-2:the expression of PACS-2 was elevated in the APP group compared with the WT group and decreased in the TSG group compared with the APP group,with statistically significant differences(P<0.05).Conclusion PACS-2 has an important role in the development of AD,and its upregulation may promote the development of AD.The cerebroprotective drug TSG may exert cytoprotective effects by downregulating PACS-2 to inhibit apoptosis and improve mitochondrial function in AD model cells.