Sulforaphane protects against ethanol-induced oxidative stress and apoptosis in neural crest cells by the induction of Nrf2-mediated antioxidant response
Sulforaphane protects against ethanol-induced oxidative stress and apoptosis in neural crest cells by the induction of Nrf2-mediated antioxidant response
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DOI：
10.1111/bph.12133
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发表时间：
2013-05-01
影响因子：
7.3
通讯作者：
Chen, S-Y
中科院分区：
文献类型：
--
作者：
Chen, X.;Liu, J.;Chen, S-Y
背景和目的核因子红细胞2相关因子（Nuclear factor erythroid 2-related factor，Nrf 2）是一种上调多种抗氧化基因并保护细胞免受氧化损伤的转录因子。本研究旨在确定D-L-萝卜硫素（SFN）是否可以保护神经嵴细胞（NCC）（一种与胎儿酒精谱系障碍有关的乙醇敏感细胞群）免受乙醇诱导的细胞凋亡，以及SFN的保护作用是否是通过诱导Nrf 2介导的抗氧化反应来介导的。将对照、SFN处理的或Nrf 2-siRNA转染的NCC暴露于乙醇。Nrf 2激活，Nrf 2下游抗氧化蛋白的表达和活性，活性氧的产生和细胞凋亡在控制和乙醇暴露的NCC中进行了测定。NCC单独暴露于SFN显著增加了Nrf 2激活和Nrf 2下游抗氧化剂的表达以及抗氧化酶的活性。用SFN沿着乙醇处理NCC显著降低乙醇诱导的氧化应激和凋亡。与此相反，敲低Nrf 2的siRNA显着增加的敏感性NCCs乙醇诱导的氧化应激和凋亡。Nrf 2信号的抑制也显着减少了SFN介导的抗氧化反应，并取消了SFN对乙醇诱导的氧化应激和细胞凋亡的保护作用。结论和影响这些结果表明，Nrf 2介导的抗氧化反应起着重要的作用，在敏感性的NCCs乙醇诱导的氧化应激和细胞凋亡和SFN对乙醇诱导的氧化应激和细胞凋亡的Nrf 2信号的诱导介导的保护。
Background and Purpose Nuclear factor erythroid 2-related factor (Nrf2) is a transcription factor that up-regulates a diverse array of antioxidant genes and protects cells from oxidative damage. This study is designed to determine whether D-L-sulforaphane (SFN) can protect neural crest cells (NCCs), an ethanol-sensitive cell population implicated in fetal alcohol spectrum disorders, against ethanol-induced apoptosis and whether protective effects of SFN are mediated by the induction of Nrf2-mediated antioxidant response. Experimental Approach Control, SFN-treated or Nrf2-siRNA transfected NCCs were exposed to ethanol. Nrf2 activation, the expression and activities of Nrf2 downstream antioxidant proteins, reactive oxygen species generation and apoptosis were determined in control and ethanol-exposed NCCs. Key Results Exposure of NCCs to SFN alone significantly increased Nrf2 activation and the expression of Nrf2 downstream antioxidants as well as the activities of the antioxidant enzymes. Treatment of NCCs with SFN along with ethanol significantly decreased ethanol-induced oxidative stress and apoptosis. In contrast, knockdown of Nrf2 by siRNA significantly increased the sensitivity of NCCs to ethanol-induced oxidative stress and apoptosis. Suppression of Nrf2 signalling in NCCs also significantly diminished SFN-mediated antioxidant response and abolished the protective effects of SFN on ethanol-induced oxidative stress and apoptosis. Conclusions and Implications These results demonstrated that Nrf2-mediated antioxidant response plays an important role in the susceptibility of NCCs to ethanol-induced oxidative stress and apoptosis and that the protection of SFN against ethanol-induced oxidative stress and apoptosis in NCCs is mediated by the induction of Nrf2 signalling.