Protective effect of 3H‐1, 2‐dithiole‐3‐thione on cellular model of Alzheimer's disease involves Nrf2/ARE signaling pathway
Protective effect of 3H‐1, 2‐dithiole‐3‐thione on cellular model of Alzheimer's disease involves Nrf2/ARE signaling pathway
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DOI：
10.1016/j.ejphar.2016.12.013
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发表时间：
2017-01
影响因子：
5
通讯作者：
Lan Wang;Min Wang;Jing Hu;W. Shen;Junjie Hu;Yi Yao;Xi-feng Wang;Curimbacus M Afzal;Rong Ma;Gang Li
中科院分区：
文献类型：
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作者：
Lan Wang;Min Wang;Jing Hu;W. Shen;Junjie Hu;Yi Yao;Xi-feng Wang;Curimbacus M Afzal;Rong Ma;Gang Li
核因子红细胞2相关因子2（Nrf 2）是编码解毒和抗氧化酶的一系列基因的主要调节因子。3 H-1，2-二硫杂环戊烯-3-酮（D3 T）是一种有效的自由基清除剂，能够激活Nrf 2信号通路。本研究以N2 a/APPswe细胞作为阿尔茨海默病（Alzheimer's disease，AD）细胞模型，探讨D3 T对N2 a/APPswe细胞的保护作用及其可能机制。我们的实验表明，D3 T能够减少活性氧的产生，增加MMP水平以及降低MDA含量。40 μ MD 3 T处理N2 a/APPswe细胞24 h后，Aβ水平明显降低。本研究还发现，D3 T可显著上调N2 a/APPswe细胞Nrf 2 mRNA和蛋白表达，并随后增强HO-1和NQO 1 mRNA的表达。同时，通过小干扰RNA下调Nrf 2的表达，取消了D3 T的细胞保护作用。综上所述，这些结果表明，D3 T在体外模型中提供神经保护，因此可能是AD治疗的潜在补充。
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a major regulator for a battery of genes encoding detoxifying and antioxidative enzymes. 3H-1, 2-dithiole-3-thione (D3T), a potent free radical scavenger, is able to activate Nrf2 signaling pathway. In the present study, N2a/APPswe cells were used as the Alzheimer's disease (AD) cellular model and we investigated the protective effect of D3T on N2a/APPswe cells and the potential mechanisms. Our assays demonstrated that D3T was able to attenuate reactive oxygen species generation, increase MMP level as well as decrease MDA content. Furthermore, treatment of the cells with 40 μM D3T for 24 h, showed significant suppression of Aβ level in N2a/APPswe cells. The current study also found that D3T significantly upregulated the Nrf2 mRNA level and protein expression, and subsequently enhanced mRNA expression of HO-1 and NQO1 in N2a/APPswe cells. Meanwhile, down-regulation of Nrf2 by small interference RNA abolished cytoprotection of D3T. Taken together, these results demonstrate that D3T provides neuroprotection in vitro model and therefore may be a potential complement for AD therapy.