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通过激活 Nrf2 核转位,萝卜硫素抑制 6-羟多巴胺诱导的内质网应激。

Inhibition of 6-hydroxydopamine-induced endoplasmic reticulum stress by sulforaphane through the activation of Nrf2 nuclear translocation.

机构信息

Deparment of Emergency, the People's Hospital of Guang Du District, Kunming 650200, PR China.

出版信息

Mol Med Rep. 2012 Jul;6(1):215-9. doi: 10.3892/mmr.2012.894. Epub 2012 Apr 27.

DOI:10.3892/mmr.2012.894
PMID:22552270
Abstract

Endoplasmic reticulum (ER) stress plays a key role in the development of neurodegenerative diseases, including Parkinson's disease (PD). Sulforaphane (SF) is a natural drug derived from isothiocyanate found in cruciferous vegetables. Although there are reports indicating that SF is a potential candidate for PD treatment, there have been no reports on the effects of SF on ER stress in PD. In this study, we investigated the cytoprotective effects of SF on 6-hydroxydopamine (6-OHDA)-induced ER stress in rat PC12 cells. Pre-treatment with SF elicited cytoprotection against 6-OHDA-induced cytotoxicity. Consistent with its cytoprotective action, SF significantly inhibited subsequent ER stress, including the expression of Bip and the C/EBP homologous protein. We also found that transfection with NF-E2-related factor-2 (Nrf2) siRNA reversed the inhibitory effects of SF on 6-OHDA-induced ER stress responses. In conclusion, our results show that SF can prevent ER stress response induced by 6-OHDA through the activation of Nrf2. SF may be a therapeutic candidate for the treatment of ER stress-associated neural diseases, including PD.

摘要

内质网应激在神经退行性疾病的发展中起着关键作用,包括帕金森病(PD)。萝卜硫素(SF)是一种天然药物,来源于十字花科蔬菜中的异硫氰酸盐。尽管有报道表明 SF 是 PD 治疗的潜在候选药物,但尚无关于 SF 对 PD 中内质网应激影响的报道。在这项研究中,我们研究了 SF 对大鼠 PC12 细胞中 6-羟多巴胺(6-OHDA)诱导的内质网应激的细胞保护作用。SF 的预处理可诱发对 6-OHDA 诱导的细胞毒性的细胞保护作用。与它的细胞保护作用一致,SF 显著抑制了随后的内质网应激,包括 Bip 和 C/EBP 同源蛋白的表达。我们还发现,用 NF-E2 相关因子-2(Nrf2)siRNA 转染逆转了 SF 对 6-OHDA 诱导的内质网应激反应的抑制作用。总之,我们的结果表明,SF 可以通过激活 Nrf2 来预防 6-OHDA 诱导的内质网应激反应。SF 可能是治疗与内质网应激相关的神经疾病,包括 PD 的治疗候选药物。

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