Ferristatin II Inhibits Ferroptosis by Regulating the Bone Morphogenetic Protein 6/SMAD Signaling Pathway in HepG2 Cells

IF 2.9 4区医学 Q1 Medicine

Journal of biomedical nanotechnology Pub Date : 2023-11-01 DOI:10.1166/jbn.2023.3705

Yiyu Hong, Zhaozhong Xu, Yantao Zheng, Jing Liu, Zhenhui Huang, Jiasong Chen, Yao Zhang, Bin Liu

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Abstract

The aim of this study was to investigate the protective effect of Ferristatin II (Fer II) on ferric ammonium citrate (FAC)-induced ferroptosis and explore its mechanism by performing experiments in vitro. The cell viability of Fer II in the treatment of FAC-induced ferroptosis was investigated by MTT, measuring the concentrations of Fe2+ and MDA and the activity of CSH-PX. We further measured the protein expression of hepcidin (Hepc), TfR1, BMP6, p-Smad1 and p-Smad5 using Western blotting. The gene expression level of Hepc was significantly increased and the protein expression levels of p-SMAD1 and p-SMAD5 were also significantly up-regulated after the coordinated intervention of Fer II and BMP. The results showed that cell viability was increased after treatment with Fer II. The concentrations of Fe2+ and MDA revealed that Fer II decreased hepatocyte ferroptosis induced by FAC. The Western blot results also showed that Fer II up-regulated the protein expression of Hepc and down-regulated protein expression of TfR1, BMP6, p-Smad1 and p-Smad5. Further results showed that Fer II and BMP6 synergistically promoted Hepc secretion and up-regulated the protein expression levels of Smad1 and p-Smad5. Fer II alleviated FAC-induced ferroptosis in HepG2 cells by regulating the BMP6/SMAD pathway, suggesting a new therapeutic approach for hepatocyte protection.

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铁锈素 II 通过调节 HepG2 细胞中的骨形态发生蛋白 6/SMAD 信号通路抑制铁蜕变

本研究旨在通过体外实验研究铁锈素Ⅱ（FerⅡ）对柠檬酸铁铵（FAC）诱导的铁中毒的保护作用及其机制。我们用 MTT 检测了 Fer II 在治疗 FAC 诱导的铁中毒中的细胞活力，测量了 Fe2+ 和 MDA 的浓度以及 CSH-PX 的活性。我们还用 Western 印迹法测定了肝素（Hepc）、TfR1、BMP6、p-Smad1 和 p-Smad5 的蛋白表达。在 Fer II 和 BMP 的协同干预下，Hepc 的基因表达水平明显提高，p-SMAD1 和 p-SMAD5 的蛋白表达水平也明显上调。结果表明，Fer II 处理后细胞活力增加。Fe2+和MDA的浓度显示，Fer II降低了FAC诱导的肝细胞铁变态反应。Western 印迹结果还显示，Fer II 上调了 Hepc 的蛋白表达，下调了 TfR1、BMP6、p-Smad1 和 p-Smad5 的蛋白表达。进一步的结果表明，Fer II 和 BMP6 协同促进了 Hepc 的分泌，并上调了 Smad1 和 p-Smad5 的蛋白表达水平。Fer II通过调节BMP6/SMAD通路缓解了FAC诱导的HepG2细胞铁变态反应，为保护肝细胞提供了一种新的治疗方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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