S1PR2 Regulates Mitochondrial Function through the AKT/mTOR Pathway to Promote Aβ25-35 Damage of SH-SY5Y Cells
10.13865/j.cnki.cjbmb.2024.08.1119
- VernacularTitle:1-磷酸鞘氨醇受体2通过AKT/mTOR通路调节线粒体功能参与Aβ25-35诱导的人神经母细胞瘤细胞SH-SY5Y损伤
- Author:
Zhi-Qiang XIAO
1
;
Liu YANG
;
Rui HUANG
;
Bin HUANG
;
Xiao-Jia LI
;
Xiao-Ping WANG
Author Information
1. 成都中医药大学神经内科,成都 610075
- Keywords:
sphingosine-1-phosphate receptor 2(S1PR2);
amyloid β protein25-35(Aβ25-35);
Alzheimer's disease(AD);
mitochondrial function;
AKT/mTOR pathway
- From:
Chinese Journal of Biochemistry and Molecular Biology
2024;40(10):1453-1461
- CountryChina
- Language:Chinese
-
Abstract:
Alzheimer's disease(AD)is a neurodegenerative disease with age-related cognitive decline.Sphingosine-1-phosphate receptor 2(S1PR2)is involved in a variety of cellular processes and has been shown to play an important role in nervous system development.This study aimed to investigate the effects and possible mechanism of S1PR2 on Aβ25-35 induced cell model damage of AD.In this study,SH-SY5Y cells were induced by Aβ25-35 to construct a cell damage model,and the expression of S1PR2 in cells was interfered by targeting sequence.The protein and gene expression levels of S1PR2 were detected by Western blot and RT-PCR.It was found that the expression of S1PR2 was significantly increased at mR-NA and protein levels in Aβ25-35-induced SH-SY5Y cell model(P＜0.01),and its expression was signifi-cantly decreased after S1PR2 intervention(P＜0.001).The cell proliferation activity was detected by CCK8,and apoptosis was detected by flow cytometry.The results showed that the proliferation activity of Aβ25-35 induced SH-SY5Y cells was significantly increased,and apoptosis was decreased after S1PR2 in-tervention(P＜0.01).The protein levels of APP,Tau,p-Tau,and PSD95 in cells were detected by Western blot to analyze the effect of S1PR2 on the pathology of AD.It was found that after S1PR2 inter-vention,the expressions of APP,Tau,and p-Tau in the AD cell model were significantly decreased(P＜0.001),and the expression of synaptic protein PSD95 was increased(P＜0.001),which could signifi-cantly improve the pathological damage in Aβ25-35-induced SH-SY5Y cell model.In addition,ATP pro-duction was detected by the kit,and ROS content and mitochondrial membrane potential were detected by flow cytometry to analyze the mitochondrial function.Results found that ATP production and mitochondri-al membrane potential was significantly decreased,whereas the ROS content was increased in Aβ25 35 in-duced SH-SY5Y cells(P＜0.001).Intervention with S1PR2 significantly increased ATP production and mitochondrial membrane potential,but decreased ROS content(P＜0.001).Finally,the protein levels of the AKT/mTOR pathway were detected by Western blot.The results showed that S1PR2 significantly in-hibited the activation of the AKT/mTOR pathway induced by Aβ25-35 in SH-SY5Y cells.In conclusion,S1PR2 may be involved in the pathogenesis of Aβ25-35-induced SH-SY5Y cells by promoting mitochondrial function through the AKT/mTOR pathway.
