中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (6): 1105-1110.doi: 10.4103/1673-5374.300461

• 原著:退行性病与再生 • 上一篇    下一篇

杨梅素可抑制铁调素表达减轻鱼藤酮诱导MES23.5细胞的毒性

  


  • 出版日期:2021-06-15 发布日期:2020-12-31
  • 基金资助:

    国家自然科学基金(81671249),山东省自然科学基金(ZR2016CM04

Myricetin reduces cytotoxicity by suppressing hepcidin expression in MES23.5 cells

Han Deng1, #, Shang Liu1, #, Dong Pan1, Yi Jia1, Ze-Gang Ma1, 2, *   

  1. 1 Department of Physiology, School of Basic Medicine, Qingdao University, Qingdao, Shandong Province, China;  2 Institute of Brain Science and Disorders, Qingdao University, Qingdao, Shandong Province, China
  • Online:2021-06-15 Published:2020-12-31
  • Contact: Ze-Gang Ma, PhD, mazegang@126.com.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, No. 81671249; and the Natural Science Foundation of Shandong Province of China, No. ZR2016CM04 (both to ZGM). 

摘要:

研究表明黑质中铁积累可能与帕金森病中多巴胺神经元变性有关。因此减缓细胞中铁积累是延迟和治疗帕金森病的关键。杨梅素具有抗氧化、抗凋亡、抗炎和铁螯合作用,但其在介导神经保护方面的机制还有待研究。实验以400nM鱼藤酮干预MES23.5细胞24h建立帕金森病体外模型,造模前1h起以1 × 10-6 M杨梅素干预进行治疗。结果发现杨梅素可减轻鱼藤酮诱导的细胞活性下降,同时抑制细胞内活性氧的产生,并恢复线粒体膜电位。此外杨梅素还能抑制鱼藤酮诱导的铁调素基因转录,并部分抑制铁转运蛋白1 mRNA和蛋白的表达,还抑制STAT3和SMAD1的活化。表明杨梅素可通过有效抑制铁调素的表达来防止铁积累,从而减轻鱼藤酮对MES23.5细胞的毒性作用,且这种作用是通过STAT3和SMAD1信号通路来介导的。

https://orcid.org/0000-0001-6084-2646 (Ze-Gang Ma)

关键词: 帕金森病, 类黄酮, 铁调素, 铁, 鱼藤酮, 体外, 因子, 通路

Abstract: Multiple studies implicate iron accumulation in the substantia nigra in the degeneration of dopaminergic neurons in Parkinson’s disease. Indeed, slowing of iron accumulation in cells has been identified as the key point for delaying and treating Parkinson’s disease. Myricetin reportedly plays an important role in anti-oxidation, anti-apoptosis, anti-inflammation, and iron chelation. However, the mechanism underlying its neuroprotection remains unclear. In the present study, MES23.5 cells were treated with 1 × 10–6 M myricetin for 1 hour, followed by co-treatment with 400 nM rotenone for 24 hours to establish an in vitro cell model of Parkinson’s disease. Our results revealed that myricetin alleviated rotenone-induced decreases in cell viability, suppressed the production of intracellular reactive oxygen species, and restored mitochondrial transmembrane potential. In addition, myricetin significantly suppressed rotenone-induced hepcidin gene transcription and partly relieved rotenone-induced inhibition of ferroportin 1 mRNA and protein levels. Furthermore, myricetin inhibited rotenone-induced phosphorylation of STAT3 and SMAD1 in MES23.5 cells. These findings suggest that myricetin protected rotenone-treated MES23.5 cells by potently inhibiting hepcidin expression to prevent iron accumulation, and this effect was mediated by alteration of STAT3 and SMAD1 signaling pathways. 

Key words: factor, flavonoid, hepcidin, in vitro, iron, Parkinson’s disease, pathways, rotenone