Scholarlink

<p>The impact of empagliflozin on OGD/R-induced ferroptosis in neurons is still unclear. This study aims to explore whether ferroptosis is associated with OGD/R-induced neuronal injury and the effect of empagliflozin on the ferroptosis effect of OGD/R-treated neurons. Western blotting, immunofluorescence, and RT-qPCR were used to detect the protein and mRNA levels of GPX4, Nrf2, and HO-1. ELISA, flow cytometry, and confocal microscopy were applied to analyze oxidative stress. Transmission electron microscopy and CCK-8 were used to determine the degree of ferroptosis in neurons. We observed a reduction in GPX4 levels and an increase in Nrf2 and HO-1 levels in OGD/R related neurons HT-22 cells. Notably, OGD/R elevates lipid peroxidation accumulation, ROS, Fe<sup>2+</sup>, and MDA levels while reducing GSH levels and decreasing mitochondrial membrane potential, leading to abnormal mitochondrial structure and eventual neuronal ferroptosis. Empagliflozin activates the Nrf2/HO-1 signaling pathway, enhances cellular antioxidant capacity, inhibits lipid peroxidation in OGD/R-treated neurons, and restores cellular iron homeostasis. In addition, empagliflozin can significantly reverse ferroptosis in OGD/R-treated neurons, and overexpression of Nrf2 combined with empagliflozin further inhibits ferroptosis in OGD/R-treated neurons. These results suggest that ferroptosis may be an essential cause of OGD/R-related neuron death. Empagliflozin exhibits a protective influence against OGD/R-induced ferroptosis by activating the Nrf2/HO-1 pathway.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Empagliflozin Inhibits Neuronal Ferroptosis Induced by Oxygen–Glucose Deprivation/Reoxygenation by Activating the Nrf2/HO-1 Pathway

  • 期刊论文

  • 发表日期：

    2025年3月5日

查看全文
  • Jialiang Ma,
  • Hongxia Wang,
  • Juan Jia,
  • Ting Tao,
  • Lingzhi Shan,
  • Shougang Sun,
  • Manxia Wang

摘要

The impact of empagliflozin on OGD/R-induced ferroptosis in neurons is still unclear. This study aims to explore whether ferroptosis is associated with OGD/R-induced neuronal injury and the effect of empagliflozin on the ferroptosis effect of OGD/R-treated neurons. Western blotting, immunofluorescence, and RT-qPCR were used to detect the protein and mRNA levels of GPX4, Nrf2, and HO-1. ELISA, flow cytometry, and confocal microscopy were applied to analyze oxidative stress. Transmission electron microscopy and CCK-8 were used to determine the degree of ferroptosis in neurons. We observed a reduction in GPX4 levels and an increase in Nrf2 and HO-1 levels in OGD/R related neurons HT-22 cells. Notably, OGD/R elevates lipid peroxidation accumulation, ROS, Fe2+, and MDA levels while reducing GSH levels and decreasing mitochondrial membrane potential, leading to abnormal mitochondrial structure and eventual neuronal ferroptosis. Empagliflozin activates the Nrf2/HO-1 signaling pathway, enhances cellular antioxidant capacity, inhibits lipid peroxidation in OGD/R-treated neurons, and restores cellular iron homeostasis. In addition, empagliflozin can significantly reverse ferroptosis in OGD/R-treated neurons, and overexpression of Nrf2 combined with empagliflozin further inhibits ferroptosis in OGD/R-treated neurons. These results suggest that ferroptosis may be an essential cause of OGD/R-related neuron death. Empagliflozin exhibits a protective influence against OGD/R-induced ferroptosis by activating the Nrf2/HO-1 pathway.