Polysulfide protects midbrain dopaminergic neurons from MPP+-induced degeneration via enhancement of glutathione biosynthesis.
Polysulfide protects midbrain dopaminergic neurons from MPP+-induced degeneration via enhancement of glutathione biosynthesis.
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DOI：
10.1016/j.jphs.2018.04.004
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发表时间：
2018-05
影响因子：
3.5
通讯作者：
Shuhei Takahashi;A. Hisatsune;Y. Kurauchi;T. Seki;H. Katsuki
中科院分区：
文献类型：
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作者：
Shuhei Takahashi;A. Hisatsune;Y. Kurauchi;T. Seki;H. Katsuki
多硫化物是内源性含硫分子种类，可以调节各种细胞功能。在这里，我们检查了外源性应用于大鼠中脑切片培养物的多硫化物的效果，以解决其潜在的神经保护作用。浓度为 10 μM 或更高的 Na2S3 可防止 1-甲基-4-苯基吡啶鎓 (MPP+) 诱导的多巴胺能神经元损失。 10 μM 的 Na2S4 还可以保护多巴胺能神经元免受 MPP+细胞毒性的影响，而相同浓度的 Na2S 和 Na2S2 没有显着效果。我们还发现，通过 2',7'-二氯荧光素荧光检测，Na2S3 (10 μM) 可以阻止 MPP+ 诱导的细胞内活性氧的增加。此外，Na2S3的保护作用被谷胱甘肽合成抑制剂L-丁硫氨酸亚砜亚胺所消除。在神经元（SH-SY5Y 细胞）和神经胶质细胞（C6 细胞）的细胞模型中，Na2S3（30 和 100 μM）增加了编码谷氨酸半胱氨酸连接酶（谷胱甘肽生物合成的限速酶）亚基的 mRNA 表达。一致地，Na2S3 增加了细胞中总谷胱甘肽的含量，并且该效果在 SH-SY5Y 细胞中比在 C6 细胞中更显着。这些结果表明，多硫化物是优于单硫物质（例如 H2S 和 HS−）的有效神经保护剂，并且多硫化物的神经保护作用是通过谷胱甘肽生物合成的上调介导的。
Polysulfides are endogenous sulfur-containing molecular species that may regulate various cellular functions. Here we examined the effect of polysulfides exogenously applied to rat midbrain slice cultures, to address their potential neuroprotective actions. Na2S3at concentrations of 10 μM or higher prevented 1-methyl-4-phenylpyridinium (MPP+)-induced loss of dopaminergic neurons. Na2S4at 10 μM also protected dopaminergic neurons from MPP+cytotoxicity, whereas Na2S and Na2S2at the same concentration had no significant effect. We also found that Na2S3(10 μM) prevented MPP+-induced increase in intracellular reactive oxygen species as detected by 2′,7′-dichlorofluorescein fluorescence. In addition, the protective effect of Na2S3was abolished byl-buthionine sulfoximine, an inhibitor of glutathione synthesis. In cellular models of neurons (SH-SY5Y cells) and glial cells (C6 cells), Na2S3(30 and 100 μM) increased expression of mRNAs encoding the subunits of glutamate cysteine ligase, the rate-limiting enzyme for glutathione biosynthesis. Consistently, the cellular content of total glutathione was increased by Na2S3, and the effect was more prominent in SH-SY5Y cells than in C6 cells. These results suggest that polysulfides are efficient neuroprotectants superior to monosulfur species such as H2S and HS−, and that the neuroprotective effect of polysulfides is mediated by upregulation of glutathione biosynthesis.