<br>富含鸟嘌呤的 RNA 序列结合因子 1 通过 GPX4 信号通路调节大鼠脊髓损伤后神经元铁死亡,Brain Research

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富含鸟嘌呤的 RNA 序列结合因子 1 通过 GPX4 信号通路调节大鼠脊髓损伤后神经元铁死亡
Brain Research ( IF 2.7 ) Pub Date : 2023-07-26 , DOI: 10.1016/j.brainres.2023.148497
Jin Wang ₁ , Jinqi Lu ₂ , Yi Zhu ₁ , Qun Huang ₁ , Qi Gu ₁ , Shoujin Tian ₁ , Jianfei Ge ₁ , Xiaolong Lin ₁ , Weiping Sha ₁

Affiliation

脊髓损伤（SCI）可引发多种形式的神经元细胞死亡。其中，铁死亡是一种特别重要的细胞死亡类型，因为它具有铁过载依赖性脂质过氧化调节机制。富含鸟嘌呤的 RNA 序列结合因子 1 （GRSF1）是一种 RNA 结合蛋白，与细胞衰老、线粒体功能、氧化应激、红细胞生成和胚胎脑发育有关。然而，GRSF1 在 SCI 后神经元铁死亡中的功能仍不清楚。在这里，我们在体内建立了 SCI 大鼠模型，并通过抑制和过表达 GRSF1 来评价 GRSF1 对神经元铁死亡的功能。我们首先验证了 GRSF1 和 GPX4 在 SCI 后不同时间点的蛋白表达。根据表达变化，我们选择 SCI 后 3 d 来评估 GRSF1 对铁死亡的影响。我们发现 GRSF1 在 SCI 后表达降低。此外，GRSF1 主要定位于神经元的细胞质中。结果还显示，GRSF1 的过表达促进了 SCI 后神经功能的恢复。进一步研究显示，GRSF1 可能通过调节 GPX4 蛋白表达水平来减弱神经元铁死亡。总之，我们的研究结果表明，GRSF1 减轻 SCI 损伤，减少神经元铁死亡，并通过 GPX4 促进功能恢复。

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Guanine-rich RNA sequence binding factor 1 regulates neuronal ferroptosis after spinal cord injury in rats via the GPX4 signaling pathway

Spinal cord injury (SCI) can trigger multiple forms of neuronal cell death. Among these, ferroptosis stands out as a particularly important style of cell death due to its iron overload-dependent lipid peroxidative regulatory mechanism. The guanine-rich RNA sequence binding factor 1 (GRSF1) is an RNA-binding protein that has been implicated in cellular senescence, mitochondrial function, oxidative stress, erythropoiesis, and embryonic brain development. However, the function of GRSF1 in neuronal ferroptosis after SCI remains unclear. Here, we established a SCI rat model in vivo and evaluated the function of GRSF1 on neuronal ferroptosis by inhibiting and overexpressing GRSF1. We firstly verified the protein expression of GRSF1 and GPX4 at different time points after SCI. According of changes in expression, we chose 3 d post SCI to assess the effect of GRSF1 on ferroptosis. We found that GRSF1 expression decreased after SCI. In addition, GRSF1 was mainly localized in the cytoplasm of neurons. The results also showed that overexpression of GRSF1 promoted recovery of neurological functional after SCI. Further investigation revealed that GRSF1 might attenuate neuronal ferroptosis by regulating the GPX4 protein expression levels. In summary, our findings indicate that GRSF1 attenuates injury in SCI and reduces neuron ferroptosis and promotes functional recovery via GPX4.

更新日期：2023-07-26

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