Sulforaphane Protects Against Ethanol-Induced Apoptosis in Human Neural Crest Cells Through Diminishing Ethanol-Induced Hypermethylation at the Promoters of the Genes Encoding the Inhibitor of Apoptosis Proteins.
Sulforaphane Protects Against Ethanol-Induced Apoptosis in Human Neural Crest Cells Through Diminishing Ethanol-Induced Hypermethylation at the Promoters of the Genes Encoding the Inhibitor of Apoptosis Proteins.
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DOI：
10.3389/fcell.2021.622152
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发表时间：
2021
影响因子：
5.5
通讯作者：
Chen SY
中科院分区：
文献类型：
--
作者：
Li Y;Fan H;Yuan F;Lu L;Liu J;Feng W;Zhang HG;Chen SY
神经嵴细胞（NCC）是一种多能祖细胞群，对乙醇敏感，与胎儿酒精谱系障碍（FASD）有关。研究表明，萝卜硫素（SFN）可以防止乙醇诱导的NCC细胞凋亡。本研究旨在探讨乙醇暴露是否可以通过表观遗传学抑制抗凋亡基因的表达诱导人NCCs（hNCCs）凋亡，以及SFN是否可以恢复抗凋亡基因的表达，并防止乙醇暴露的hNCCs凋亡。我们发现，乙醇暴露导致DNMT3a的表达和DNMTs的活性显著增加。SFN处理减弱了乙醇诱导的DNMT 3a上调，并显著降低了乙醇暴露的hNCC中DNMT的活性。我们还发现，乙醇暴露诱导的两个抑制剂的凋亡蛋白（IAP），NAIP和XIAP，在hNCCs，这是防止共同治疗SFN的启动子区域的超甲基化。SFN治疗还显著减少了乙醇诱导的hNCC中NAIP和XIAP的下调。DNMT3a的敲低显著增强SFN对防止乙醇诱导的NAIP和XIAP抑制以及hNCCs中的凋亡的作用。这些结果表明，SFN可以防止乙醇诱导的hNCC中的细胞凋亡，通过防止乙醇诱导的IAP蛋白编码基因的启动子区域的高甲基化，并通过调节DNMT 3a表达和DNMT活性来减少乙醇诱导的NAIP和XIAP抑制。
The neural crest cell (NCC) is a multipotent progenitor cell population that is sensitive to ethanol and is implicated in the Fetal Alcohol Spectrum Disorders (FASD). Studies have shown that sulforaphane (SFN) can prevent ethanol-induced apoptosis in NCCs. This study aims to investigate whether ethanol exposure can induce apoptosis in human NCCs (hNCCs) through epigenetically suppressing the expression of anti-apoptotic genes and whether SFN can restore the expression of anti-apoptotic genes and prevent apoptosis in ethanol-exposed hNCCs. We found that ethanol exposure resulted in a significant increase in the expression of DNMT3a and the activity of DNMTs. SFN treatment diminished the ethanol-induced upregulation of DNMT3a and dramatically reduced the activity of DNMTs in ethanol-exposed hNCCs. We also found that ethanol exposure induced hypermethylation at the promoter regions of two inhibitor of apoptosis proteins (IAP), NAIP and XIAP, in hNCCs, which were prevented by co-treatment with SFN. SFN treatment also significantly diminished ethanol-induced downregulation of NAIP and XIAP in hNCCs. The knockdown of DNMT3a significantly enhanced the effects of SFN on preventing the ethanol-induced repression of NAIP and XIAP and apoptosis in hNCCs. These results demonstrate that SFN can prevent ethanol-induced apoptosis in hNCCs by preventing ethanol-induced hypermethylation at the promoter regions of the genes encoding the IAP proteins and diminishing ethanol-induced repression of NAIP and XIAP through modulating DNMT3a expression and DNMT activity.
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DOI：
10.1007/7651_2015_234
发表时间：
2016-01-01
期刊：
EMBRYONIC STEM CELL PROTOCOLS
影响因子：
--
作者：
Avery, John;Dalton, Stephen
通讯作者：
Dalton, Stephen
影响因子：
7.3
作者：
Chen, X.;Liu, J.;Chen, S-Y
通讯作者：
Chen, S-Y
DOI：
10.1073/pnas.040469797
发表时间：
2000-02-29
影响因子：
11.1
作者：
Holcik, M;Thompson, CS;Korneluk, RG
通讯作者：
Korneluk, RG
癌细胞中的DNA甲基化和凋亡性。
影响因子：
6
作者：
Hervouet E;Cheray M;Vallette FM;Cartron PF
通讯作者：
Cartron PF
DOI：
10.1111/acer.12082
发表时间：
2013-07
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Bekdash RA;Zhang C;Sarkar DK
通讯作者：
Sarkar DK