PGE1 triggers Nrf2/HO-1 signal pathway to resist hemin-induced toxicity in mouse cortical neurons.
PGE1 triggers Nrf2/HO-1 signal pathway to resist hemin-induced toxicity in mouse cortical neurons.
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PGE1触发Nrf2/HO-1信号通路抵抗氯化血红素诱导的小鼠皮质神经元毒性
DOI：
10.21037/atm-20-5839
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发表时间：
2021-04
影响因子：
--
通讯作者：
Ke K
中科院分区：
文献类型：
--
作者：
Shen J;Cao MS;Zhou T;Chen Y;Liang J;Song Y;Xue C;Cao MH;Ke K
前列腺素E1（PGE 1）具有多种药理学作用，如膜稳定、抗炎、血管舒张和血小板聚集抑制。我们以前已经证明，前列腺素E1对脑出血（ICH）患者有有益的影响。PGE 1对脑出血治疗有益的相关机制有待进一步探讨。本研究采用体外神经细胞凋亡模型，探讨前列腺素E1治疗脑出血的作用机制。用不同浓度的前列腺素E1预处理小鼠原代皮层神经元，然后用全血中的主要分解代谢物氯化血红素处理，以模拟临床ICH。与溶剂处理组相比，PGE 1可防止培养的皮层神经元细胞内活性氧（ROS）水平的抑制，线粒体膜电位的改善和氯化血红素诱导的细胞凋亡。ROS的减少和细胞凋亡与血红素加氧酶-1（HO-1）的表达上调有关。通过siRNA敲除核转录因子红细胞2相关因子（Nrf 2）可减弱HO-1的上调以及PGE 1的保护作用。我们的工作表明，Nrf 2/HO-1分子通路可能在PGE 1治疗脑出血患者中发挥关键作用，并可能成为新的分子靶点，从而发现新的脑出血治疗药物。
Prostaglandin E1 (PGE1) exerts various pharmacological effects such as membrane stabilization, anti-inflammatory functions, vasodilation, and platelet aggregation inhibition. We have previously demonstrated that PGE1 has a beneficial impact on patients suffering from intracerebral hemorrhage (ICH). The related mechanism underlying PGE1’s beneficial effect on ICH treatment needs further exploration. The present study elucidates the mechanism of PGE1 on ICH treatment using a neuronal apoptosis model in vitro. The mouse primary cortical neurons were pretreated with different concentrations of PGE1, followed by the treatment with hemin, the main catabolite in whole blood, to mimic the clinical ICH. Comparing with the vehicle-treated group, PGE1 prevented cultured cortical neurons from the accumulation of inhibited intracellular levels of reactive oxygen species (ROS), amelioration of mitochondrial membrane potential, and hemin-induced apoptosis. The reduction of ROS and apoptosis were associated with the up-regulation of Heme oxygenase-1 (HO-1) expression. Knockdown of nuclear transcription factor erythroid 2-related factor (Nrf2) by siRNA attenuated the upregulation of HO-1 as well as the protective effect of PGE1. Our work suggests that the Nrf2/HO-1 molecular pathway may play a crucial role in treating ICH patients with PGE1 and may represent novel molecular targets, resulting in discovering new drugs for ICH treatment.
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