中国神经再生研究(英文版) ›› 2020, Vol. 15 ›› Issue (11): 2143-2153.doi: 10.4103/1673-5374.282264

• 原著:退行性病与再生 • 上一篇    下一篇

ε-维尼非林对鱼藤酮诱导帕金森病细胞模型的神经保护:Sirt3介导Foxo3去乙酰化的意义

  

  • 出版日期:2020-11-15 发布日期:2020-08-23
  • 基金资助:

    中国国家自然科学基金( 81771271,81801710);国辽宁省教育厅科技项目(LK2016022,LK2016021)

Neuroprotective mechanisms of ε-viniferin in a rotenone-induced cell model of Parkinson’s disease: significance of SIRT3-mediated FOXO3 deacetylation

Shuo Zhang 1 , Yan Ma 2 , Juan Feng 1   

  1. 1 Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China
    2 Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China
  • Online:2020-11-15 Published:2020-08-23
  • Contact: Juan Feng, MD, PhD,juanfeng@cmu.edu.cn.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, Nos. 81771271 (to JF), 81801710 (to YM); the Science and Technology Project Funds from Education Department of Liaoning Province of China, Nos. LK2016022 (to SZ), LK2016021 (to YM).

摘要:

既往研究显示,ε-维尼非林具有抗氧化和抗炎作用,且可通过激活Sirt3/LKB1/AMPK信号通路对亨廷顿病具有神经保护作用,但其是否也对帕金森病发挥作用尚不可知。实验以3.0μM鱼藤酮暴露24h诱导建立帕金森病细胞模型,利用1.0μMε-维尼非林孵育24h进行治疗。结果可见,(1)ε-维尼非林上调了鱼藤酮暴露细胞中的Sirt3表达,而后者可促进Foxo3去乙酰化和核定位;(2)ε-维尼非林还了增加ATP的产生,并减少活性氧的生成;(3)ε-维尼非林也减轻了鱼藤酮诱导细胞中线粒体的去极化,并减少细胞凋亡,同时恢复线粒体稳态相关蛋白的表达;(4)但在鱼藤酮和ε-维尼非林干预前,预先以Sirt3或Foxo3 shRNA转染细胞,细胞中上述变化会被逆转;(5)说明ε-维尼非林可通过增强Sirt3可介导的Foxo3去乙酰化,发挥抗氧化应激作用,并维持线粒体稳态,从而抑制鱼藤酮诱导细胞的凋亡,可能成为治疗帕金森病新的药物选择思路。

orcid: 0000-0002-1815-7036 (Juan Feng)

关键词:

ε-维尼非林, 帕金森病, Sirt3, Foxo3, 线粒体稳态, 自噬, 去乙酰化, 氧化应激

Abstract: Trans-(-)-ε-viniferin (ε-viniferin) has antioxidative and anti-inflammatory effects. It also has neuroprotective effects in Huntington’s disease by activating the SIRT3/LKB1/AMPK signaling pathway; however, it remains unknown whether ε-viniferin also has a neuroprotective role in Parkinson’s disease. A Parkinson’s disease cell model was induced by exposing SH-SY5Y cells to 3.0 μM rotenone for 24 hours, and cells were then treated with 1.0 μM ε-viniferin for 24 hours. Treatment with ε-viniferin upregulated SIRT3 expression, which promoted FOXO3 deacetylation and nuclear localization. ε-Viniferin also increased ATP production and decreased reactive oxygen species production. Furthermore, ε-viniferin treatment alleviated rotenone-induced mitochondrial depolarization and reduced cell apoptosis, and restored the expression of mitochondrial homeostasis-related proteins. However, when cells were transfected with SIRT3 or FOXO3 shRNA prior to rotenone and ε-viniferin treatment, these changes were reversed. The results from the present study indicate that ε-viniferin enhances SIRT3-mediated FOXO3 deacetylation, reduces oxidative stress, and maintains mitochondrial homeostasis, thus inhibiting rotenone-in- duced cell apoptosis. ε-Viniferin may therefore be a promising treatment strategy for Parkinson’s disease.

Key words: deacetylation, FOXO3, mitochondrial homeostasis, mitophagy, oxidative stress, Parkinson’s disease, SIRT3, ε-viniferin