| BML-284激活Wnt/β-catenin通路对铝致PC12细胞铁死亡的影响 |
| 投稿时间：2025-04-23 修订日期：2025-05-24 点此下载全文 |
| 引用本文：杨伊哲,张佳芬,周婷,梁瑞峰.BML-284激活Wnt/β-catenin通路对铝致PC12细胞铁死亡的影响[J].医学研究杂志,2025,54(10):93-98 |
| DOI：
10.11969/j.issn.1673-548X.2025.10.017 |
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| 基金项目:兵器工业卫生研究所含铝材料毒性机理研究项目(2024-12-035)；细胞生理学教育部重点实验室(山西医科大学)开放基金资助项目(CELLPHYSIOL/SXMU-2021-16)；山西省省级应用基础研究计划项目(201801D121314) |
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| 中文摘要:目的 探讨CID11210285盐酸盐(Wnt agonist 1, AMBMP, BML-284)经Wnt/β-连环蛋白(Wnt/β-catenin)通路调控铝致神经元铁死亡的可能作用机制,为进一步研究铝致神经元死亡的作用机制提供理论依据。方法 以大鼠肾上腺嗜铬细胞瘤PC12细胞为研究对象,在CCK-8法确定麦芽酚铝、BML-284染毒浓度后分为4组,即对照组、Al(mal)3组、BML-284组和Al(mal)3+BML-284组,采用试剂盒检测PC12细胞内铁离子、谷胱甘肽(glutathione,GSH)、活性氧(reactive oxygen species,ROS)和丙二醛(malondialdehyde,MDA)含量,采用Western blot法测定氧化损伤相关蛋白谷胱甘肽过氧化酶4(glutathione peroxidase 4,GPX4)、溶质载体家族7成员11(solute carrier family 7member 11,SLC7A11)及通路相关蛋白糖原合酶激酶3β(glycogen synthase kinase 3β,GSK3β)、β-连环蛋白(β-catenin)和转录因子4(transcription factor 4,TCF4)蛋白表达。采用实时荧光定量聚合酶链反应(real-time fluorescence quantitative polymerase chain reaction,RT-qPCR)法测定GPX4mRNA和SLC7A11mRNA表达。结果 与对照组比较,Al(mal)3组PC12细胞内铁离子浓度升高,GPX4蛋白表达下降；与Al(mal)3组比较,Al(mal)3+BML-284组PC12细胞内铁离子浓度下降(P＜0.05),GPX4蛋白与mRNA表达上升(P＜0.05)。结论 BML-284可能通过促进β-catenin的稳定性和核内积累,增强β-catenin/TCF复合物的形成激活Wnt/β-catenin通路,其中TCF4作为关键转录因子,β-catenin/TCF4复合物可直接结合GPX4,有效缓解Al(mal)3诱导的铁死亡。 |
| 中文关键词:铝 PC12细胞 铁死亡 Wnt/β-catenin通路 |
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| Effect of BML-284 Activating the Wnt/β-catenin Signaling Pathway on Aluminum-induced Ferroptosis in PC12 Cells. |
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| 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 further 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:control group, Al(mal)3group, BML-284group, and Al(mal)3+BML-284group. The contents of iron, glutathione (GSH), reactive oxygen 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 transcription factor 4 (TCF4) was analyzed by Western blot. The mRNA expression of GPX4 and SLC7A11 was determined by real-time fluorescence 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 mRNA 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 factor, and the β-catenin/TCF4 complex directly binds to GPX4, which effectively alleviates the Al(mal)3-induced ferroptosis. |
| keywords:Aluminum PC12 cell Ferroptosis Wnt/β-catenin pathway |
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