Emodin Protects SH-SY5Y Cells Against Zinc-Induced Synaptic Impairment and Oxidative Stress Through the ERK1/2 Pathway.
Emodin Protects SH-SY5Y Cells Against Zinc-Induced Synaptic Impairment and Oxidative Stress Through the ERK1/2 Pathway.
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DOI：
10.3389/fphar.2022.821521
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发表时间：
2022
影响因子：
5.6
通讯作者：
Tang Z
中科院分区：
文献类型：
--
作者：
Chen Q;Lai C;Chen F;Ding Y;Zhou Y;Su S;Ni R;Tang Z
锌是人体必需的微量元素，对中枢神经系统的生理功能至关重要。锌在神经元内的异常积累可引起线粒体功能障碍和氧化应激，从而导致许多脑部疾病。我们假设天然蒽醌衍生物大黄素可以通过细胞外信号调节激酶1/2 （ERK1/2）信号通路，保护病理浓度锌诱导的神经毒性，减轻氧化应激和线粒体功能障碍。用硫酸锌和不同浓度的大黄素处理人神经母细胞瘤（SH-SY5Y 26细胞），观察ETK1/2表达、氧化应激（DCFH-DA染色）、线粒体功能（JC-1染色）、脂质过氧化（4-羟基壬烯醛染色）和DNA氧化（8-羟基-2-脱氧鸟苷染色）水平的变化。在SH-SY5Y细胞中，大黄素改善了锌诱导的磷酸化ERK1/2（不是总ETK1/2）和突触蛋白（突触前SNAP 25、突触物理素和突触后PSD95）表达水平的改变。此外，大黄素抑制SH-SY5Y细胞活性氧的产生和氧化应激，促进线粒体膜电位的崩溃（ΔΨm）。综上所述，我们的研究结果表明，大黄素通过降低ERK1/2的磷酸化，减少活性氧和保护线粒体功能，使突触损伤正常化，从而发挥对锌的神经保护作用。
Zinc is an essential trace element important for the physiological function of the central nervous system. The abnormal accumulation of zinc inside neurons may induce mitochondrial dysfunction and oxidative stress, which contribute to many brain diseases. We hypothesized that natural anthraquinone derivative emodin can protect against neurotoxicity induced by pathological concentrations of zinc via the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway and alleviate oxidative stress and mitochondrial dysfunction. Human neuroblastoma (SH-SY5Y 26 cells) was treated with zinc sulfate and different concentrations of emodin, and changes in the levels of ETK1/2 expression, oxidative stress (DCFH-DA staining), mitochondrial function (JC-1 staining), lipid peroxidation (4-hydroxynonenal staining), and DNA oxidation (8-hydroxy-2-deoxyguanosine staining) were examined. Emodin ameliorated zinc-induced altered expression of levels of phosphorylated ERK1/2 (not total ETK1/2) and synaptic proteins (presynaptic SNAP 25, synaptophysin and postsynaptic PSD95) in SH-SY5Y cells. Moreover, emodin inhibited the generation of reactive oxygen species and oxidative stress and facilitated the collapse of mitochondrial membrane potential (ΔΨm) in SH-SY5Y cells. In conclusion, our results indicated that emodin exerts neuroprotective effects against zinc by normalizing synaptic impairment by decreasing the phosphorylation of ERK1/2, reducing reactive oxygen species and protecting mitochondrial function.
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