The Role of APOE4 in Regulating LRP1 on Aβ25-35-Induced Oxidative Stress and Inflammatory Response in Astrocytes
10.12259/j.issn.2095-610X.S20251103
- VernacularTitle:APOE4调控LRP1对Aβ25-35诱导的星形胶质细胞氧化应激和炎症反应的作用
- Author:
Yanping LI
1
;
Efty Tasnim FARIHA
;
Zhixing LU
;
Lingying ZHU
Author Information
1. 昆明医科大学附属延安医院神经内科,云南 昆明 650051
- Keywords:
Alzheimer's disease;
Astrocytes;
Aβ;
Oxidative stress;
Inflammatory response
- From:
Journal of Kunming Medical University
2025;46(11):18-25
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of APOE4 in regulating LRP1 and on β-amyloid protein Aβ25-35-induced oxidative stress and inflammatory response in astrocytes.Methods Human astrocytes were transfected with sh-NC,sh-APOE4,pcDNA-NC,and pcDNA-LRP1,and then induced with 10 μM Aβ25-35 for 24 h to establish an AD cell model.The roles of APOE4 and LRP1 in Aβ25-35-induced oxidative stress and inflammatory response were assessed using Western blot,flow cytometry,the detection kits of MDA,SOD,and GSH,as well as enzyme-linked immunosorbent assay(ELISA)kits for TNF-α,IL-6,and IL-1β.The protein-protein interaction between APOE4 and LRP1 was detected through co-immunoprecipitation and western blot experiments.Results Aβ25-35 induction upregulated APOE4 expression(P<0.01),promoted the levels of ROS(P<0.001),MDA(P<0.001),and inflammatory cytokines TNF-α,IL-6,and IL-1β(P<0.001)in astrocytes,while inhibited the expression of SOD,GSH,and LRP1(P<0.001).Knockdown of APOE4 or overexpression of LRP1 suppressed the Aβ25-35-induced increase in ROS,oxidative stress markers,and inflammatory cytokines in cells(P<0.05).APOE4 negatively regulated LRP1 protein expression through protein-protein interactions.The levels of ROS,MDA,and inflammatory cytokines were higher(P<0.05),and the concentrations of SOD and GSH were lower(P<0.001),in cells with simultaneous knockdown of APOE4 and LRP1 compared to those with APOE4 knockdown alone.Conclusion Knockdown of APOE4 attenuates Aβ25-35-induced oxidative stress and inflammatory response in astrocytes by upregulating LRP1.
