| SLC39A14调控HepG2细胞胰岛素抵抗的机制研究 |
| 投稿时间：2025-02-13 修订日期：2025-03-20 点此下载全文 |
| 引用本文：黎慧萍,李莹芳,黄济华,李郭乔,秦丹,梁瑜祯.SLC39A14调控HepG2细胞胰岛素抵抗的机制研究[J].医学研究杂志,2025,54(8):108-113, 128 |
| DOI：
10.11969/j.issn.1673-548X.2025.08.018 |
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| 基金项目:广西自然科学基金资助项目(2024GXNSFAA010239) |
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| 中文摘要:目的 探讨溶质载体家族39成员14(solute carrier family 39 member 14,SLC39A14)对铁过载诱导HepG2细胞胰岛素抵抗的影响及机制。方法 体外培养HepG2细胞,加入不同浓度的柠檬酸铁铵(ferric ammonium citrate,FAC)通过CCK-8检测细胞活力、钙黄绿素(Calcein-AM)检测不稳定铁池(labile iron loop,LIP)、透射电镜观察线粒体、细胞葡萄糖消耗量检测胰岛素抵抗情况、以及SLC39A14蛋白和mRNA的表达；随后加入铁死亡抑制剂(Ferrostatin-1,Fer-1)后检测活性氧(reactive oxygen species,ROS)、丙二醛(malondialdehyde,MDA)和谷胱甘肽(glutathione,GSH)；最后使用小干扰RNA(siRNA)技术敲低SLC39A14的表达,观察氧化应激及胰岛素抵抗指标是否变化。结果 FAC干预后细胞活力下降、LIP水平增加、细胞葡萄糖消耗量减少,同时上调SLC39A14蛋白和mRNA的表达。与FAC组比较,加入铁死亡抑制剂联合处理后,通过减少ROS和MDA水平、增加GSH含量等方式改善细胞内氧化应激水平,下调SLC39A14蛋白和mRNA的表达,增加葡萄糖消耗量,进而缓解胰岛素抵抗的发生。敲低SLC39A14后,FAC+SLC39A14敲低组HepG2细胞氧化应激和胰岛素抵抗水平较FAC组进一步改善。结论 FAC引起HepG2细胞胰岛素抵抗的发生,机制可能与激活SLC39A14有关。 |
| 中文关键词:铁过载 胰岛素抵抗 SLC39A14 Fer-1 铁死亡 |
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| Mechanistic on the Regulation of Insulin Resistance in HepG2 Cells by SLC39A14. |
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| Abstract:Objective To investigate the effect and mechanism of solute carrier family 39 member 14 (SLC39A14) on iron overload-induced insulin resistance in HepG2 cells. Methods HepG2 cells were cultured in vitro, and different concentrations of ferric ammonium citrate (FAC) were added to detect cell viability by CCK-8, calcein-AM was used to detect unstable iron pools (LIP), mitochondria were observed by transmission electron microscopy, and insulin resistance was detected by cellular glucose consumption, as well as the expression of SLC39A14 protein and mRNA. Subsequently, Ferrostatin-1 (Fer-1) was added to detect reactive oxygen species (ROS), malondialdehyde (MDA) and glutathione (GSH). Finally, small interfering RNA (siRNA) technology was used to knock down the expression of SLC39A14 to observe whether oxidative stress and insulin resistance indices changed. Results After FAC intervention, cell viability decreased, the LIP level increased, and glucose consumption reduced. Additionally, the protein and mRNA expression of SLC39A14 was upregulated. Compared with the FAC group, the co-treatment of FAC and Ferrostatin-1 ameliorated the intracellular oxidative stress by decreasing the levels of ROS and MDA and increasing the levels of GSH, down-regulating the protein and mRNA expression of SLC39A14, and increasing the glucose consumption, thereby alleviating the onset of insulin resistance. After knockdown of SLC39A14, the levels of oxidative stress and insulin resistance in HepG2 cells in the FAC+SLC39A14 knockdown group were further improved compared with those in the FAC group. Conclusion FAC intervention caused the development of insulin resistance in HepG2 cells by a mechanism that may be related to activation of SLC39A14. |
| keywords:Iron overload Insulin resistance SLC39A14 Fer-1 Ferroptosis |
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