Effect of BML-284 Activating the Wnt/β-catenin Signaling Pathway on Aluminum-induced Ferroptosis in PC12 Cells
10.11969/j.issn.1673-548X.2025.10.017
- VernacularTitle:BML-284激活Wnt/β-catenin通路对铝致PC12细胞铁死亡的影响
- Author:
Yizhe YANG
1
;
Jiafen ZHANG
;
Ting ZHOU
Author Information
1. 030001 太原,山西医科大学公共卫生学院
- Publication Type:Journal Article
- Keywords:
Aluminum;
PC12 cell;
Ferroptosis;
Wnt/β-catenin pathway
- From:
Journal of Medical Research
2025;54(10):93-98
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the possible mechanism by which CID11210285hydrochloride(Wnt agonist 1,AMBMP,BML-284)regulates aluminum-induced neuronal ferroptosis through the Wnt/β-catenin pathway,providing a theoretical basis for fur-ther research on the mechanisms of aluminum-induced neuronal death.Methods Taking rat adrenal pheochromocytoma PC12 cells as the research object,determined exposure concentrations of Al(mal)3 and BML-284 via CCK-8 assay and divided into four groups:con-trol group,Al(mal)3group,BML-284group,and Al(mal)3+BML-284group.The contents of iron,glutathione(GSH),reactive oxy-gen species(ROS),and malondialdehyde(MDA)in PC12 cells were detected by using the kit.The protein expression of glutathione peroxidase 4(GPX4),solute carrier family 7member 11(SLC7A11),glycogen synthase kinase 3β(GSK3β),β-catenin,and tran-scription factor 4(TCF4)was analyzed by Western blot.The mRNA expression of GPX4 and SLC7A11 was determined by real-time flu-orescence quantitative polymerase chain reaction(RT-qPCR).Results Compared with the control group,the iron ion concentration in PC12 cells of the Al(mal)3group increased,while the expression of GPX4 protein decreased.Compared with the Al(mal)3group,the iron ion concentration in PC12 cells of the Al(mal)3+BML-284 group increased(P＜0.05),and the expression of GPX4 protein and mR-NA increased(P＜0.05).Conclusion BML-284 activates the Wnt/β-catenin pathway by promoting the stability and intranuclear accumulation of β-catenin and enhancing the formation of the β-catenin/TCF complex,in which TCF4 serves as a key transcription fac-tor,and the β-catenin/TCF4 complex directly binds to GPX4,which effectively alleviates the Al(mal)3-induced ferroptosis.
