These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: [Dexmedetomidine inhibits ferroptosis of human renal tubular epithelial cells by activating the Nrf2/HO-1/GPX4 pathway].
    Author: Zhang F, Liu G.
    Journal: Nan Fang Yi Ke Da Xue Xue Bao; 2024 Jun 20; 44(6):1135-1140. PubMed ID: 38977343.
    Abstract:
    OBJECTIVE: To investigate the protective effect of dexmedetomidine (DEX) against erastin-induced ferroptosis in human renal tubular epithelial cells (HK-2 cells) and explore the underlying mechanism. METHODS: HK-2 cells were treated with erastin alone or in combination with different concentrations (2.5, 5.0 and 10 μmol/L) of DEX, and the changes in cell viability were observed using CCK-8 assay. To explore the mechanism by which DEX inhibits erastin-induced ferroptosis, HK-2 cells were treated with erastin, erastin+10 μmol/L DEX, or erastin+10 μmol/L DEX+ML385 (a Nrf2 inhibitor), after which the cell viability was assessed. The level of intracellular Fe2+ was detected by cell ferrous iron colorimetric assay kit, and flow cytometry was performed to detect reactive oxygen species (ROS); MDA and reduced glutathione assay kits were used to detect the contents of MDA and GSH in the cells; The expressions of Nrf2, HO-1 and GPX4 proteins were detected by Western blotting. RESULTS: Erastin treatment significantly inhibited the viability of the cells, decreased GSH content, and increased intracellular levels of Fe2+, ROS and MDA. The combined treatment with 10 μmol/L DEX markedly increased the viability of the cells, increased GSH content, reduced the levels of Fe2+, ROS and MDA, and upregulated the protein expressions of Nrf2, HO-1 and GPX4 in the cells. The application of ML385 obviously blocked the protective effect of DEX and caused significant inhibition of the Nrf2/HO-1/GPX4 pathway, decreased the cell viability and GSH content, and increased the levels of Fe2+, ROS and MDA in HK-2 cells. CONCLUSION: The protective effect of DEX against erastin-induced ferroptosis of HK-2 cells is probably mediated by activation of the Nrf2/HO-1/GPX4 pathway to inhibit oxidative stress. 目的: 探讨右美托咪定（DEX）对Erastin诱导的人肾小管上皮细胞（HK-2）铁死亡的保护作用及其机制。 方法: 构建Erastin诱导的HK-2细胞铁死亡模型。将HK-2细胞分为对照组、Erastin模型组、Erastin+2.5 μmol/L DEX组、Erastin+5 μmol/L DEX组、Erastin+10 μmol/L DEX组，采用CCK-8法检测细胞的存活率。将HK-2细胞分为对照组 、Erastin模型组、Erastin+10 μmol/L DEX组、Erastin+10 μmol/L DEX+ML385（Nrf2抑制剂）组。采用CCK-8法检测细胞的存活率；使用细胞亚铁比色法测试盒检测细胞内Fe2+水平的变化；应用流式细胞术检测细胞内活性氧（ROS）的含量；使用丙二醛（MDA）和还原型谷胱甘肽（GSH）试剂盒检测细胞中MDA及GSH含量；Western blotting检测细胞中核因子E2相关因子2（Nrf2）、血红素加氧酶-1（HO-1）、谷胱甘肽过氧化物酶 4（GPX4）蛋白的表达。 结果: 与对照组相比，Erastin组的细胞存活率显著被抑制（P<0.001），同时细胞中GSH含量降低（P<0.001），Fe2+、ROS以及MDA含量升高（P<0.001）；与Erastin组相比，Erastin+10 μmol/L DEX组的细胞存活率明显升高（P<0.001），10 μmol/L DEX显著升高细胞中GSH含量（P<0.001），显著降低Fe2+、ROS以及MDA含量（P<0.001），并且显著上调细胞中Nrf2、HO-1和GPX4蛋白的表达（P<0.001）。使用ML385后，Nrf2/HO-1/GPX4通路被抑制（P<0.001），细胞存活率降低（P<0.001），GSH含量降低（P<0.001），而Fe2+、ROS以及MDA含量升高（P<0.05）。 结论: DEX对Erastin诱导的HK-2细胞铁死亡具有保护作用，其机制可能是通过激活Nrf2/HO-1/GPX4通路实现抗氧化应激从而抑制铁死亡。
    [Abstract] [Full Text] [Related] [New Search]