Sulforaphane restores acetyl-histone H3 binding to Bcl-2 promoter and prevents apoptosis in ethanol-exposed neural crest cells and mouse embryos.
Sulforaphane restores acetyl-histone H3 binding to Bcl-2 promoter and prevents apoptosis in ethanol-exposed neural crest cells and mouse embryos.
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DOI：
10.1016/j.expneurol.2017.10.020
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发表时间：
2018-03
影响因子：
5.3
通讯作者：
Chen SY
中科院分区：
文献类型：
--
作者：
Yuan F;Chen X;Liu J;Feng W;Cai L;Wu X;Chen SY
萝卜硫素 (SFN) 是一种从十字花科蔬菜中提取的异硫氰酸酯。 SFN 的细胞保护特性已在与多种疾病相关的多个模型中得到证实。我们最近的研究表明，SFN 可以防止神经嵴细胞 (NCC) 中乙醇诱导的氧化应激和细胞凋亡，神经嵴细胞是一种与胎儿酒精谱系障碍 (FASD) 相关的乙醇敏感细胞群。本研究旨在检验以下假设：SFN 可以通过抑制 HDAC 并增加 Bcl-2 启动子处的组蛋白乙酰化来预防乙醇诱导的 NCC 细胞凋亡。我们发现接触 50 mM 乙醇会导致 NCC 中 HDAC 活性显着增加。 SFN 治疗降低了暴露于乙醇的 NCC 中 HDAC 的活性。我们还发现，SFN 处理显着增加了乙醇处理的 NCC 中乙酰组蛋白 H3 的表达。 ChIP-qPCR 测定显示，乙醇暴露显着降低了乙酰组蛋白 H3 与 Bcl-2 启动子的结合，而补充 SFN 则逆转了乙醇诱导的乙酰组蛋白 H3 与 Bcl-2 启动子结合的减少。此外，SFN 治疗恢复了暴露于乙醇的 NCC 中 Bcl-2 的表达，并减少了乙醇诱导的 NCC 细胞凋亡。 SFN 治疗还显着减少了体内暴露于乙醇的小鼠胚胎的细胞凋亡。这些结果表明，SFN 可以表观遗传地恢复 Bcl-2 的表达，并通过增加 Bcl-2 启动子处的组蛋白乙酰化来减弱乙醇诱导的细胞凋亡，并表明 SFN 可以通过表观遗传调控抗凋亡基因的表达来预防 FASD。
Sulforaphane (SFN) is an isothiocyanate derived from cruciferous vegetables. SFN’s cytoprotective properties have been demonstrated in several models associated with a variety of disorders. Our recent studies have shown that SFN protects against ethanol-induced oxidative stress and apoptosis in neural crest cells (NCCs), an ethanol-sensitive cell population implicated in Fetal Alcohol Spectrum Disorders (FASD). This study is designed to test the hypothesis that SFN can prevent ethanol-induced apoptosis in NCCs by inhibiting HDAC and increasing histone acetylation at the Bcl-2 promoter. We found that exposure to 50 mM ethanol resulted in a significant increase in HDAC activities in NCCs. Treatment with SFN decreased the activities of HDAC in ethanol-exposed NCCs. We also found that SFN treatment significantly increased the expression of acetyl-histone H3 in NCCs treated with ethanol. ChIP-qPCR assay revealed that ethanol exposure significantly decreased acetyl-histone H3 binding to the Bcl-2 promoter while supplementing with SFN reversed the ethanol-induced reduction in acetyl-histone H3 binding to the Bcl-2 promoter. In addition, SFN treatment restored the expression of Bcl-2 in ethanol-exposed NCCs and diminished ethanol-induced apoptosis in NCCs. Treatment with SFN also significantly diminished apoptosis in mouse embryos exposed to ethanol in vivo. These results demonstrate that SFN can epigenetically restore the expression of Bcl-2 and attenuate ethanol-induced apoptosis by increasing histone acetylation at the Bcl-2 promoter and suggest that SFN may prevent FASD through epigenetic regulation of the expression of anti-apoptotic genes.
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影响因子：
7.3
作者：
Chen, X.;Liu, J.;Chen, S-Y
通讯作者：
Chen, S-Y
DOI：
10.1038/nrg2485
发表时间：
2009-01
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
8
作者：
Hong, F;Kim, WH;Gao, B
通讯作者：
Gao, B
影响因子：
15.9
作者：
Chuang, De-Maw;Leng, Yan;Marinova, Zoya;Kim, Hyeon-Ju;Chiu, Chi-Tso
通讯作者：
Chiu, Chi-Tso
影响因子：
4.2
作者：
Ho, Emily;Clarke, John D.;Dashwood, Roderick H.
通讯作者：
Dashwood, Roderick H.