课题基金 / 基金详情

Sulforaphane-mediated epigenetic modulation of ethanol-induced apoptosis and teratogenesis

Sulforaphane-mediated epigenetic modulation of ethanol-induced apoptosis and teratogenesis
萝卜硫素介导的乙醇诱导的细胞凋亡和致畸的表观遗传调节
批准号:
8978014
负责人:
Shao-yu Chen
金额:
$22.77万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-05-15 至 2021-04-30

项目摘要

项目成果

Shao-yu Chen的其他基金

相似基金

相关文献

中文摘要
翻译
产前乙醇暴露是已知的导致智力迟钝的主要原因。越来越多的证据表明,
英文摘要
Prenatal ethanol exposure is the leading known cause of mental retardation. Growing evidence suggests that excessive cell death is a major component of the pathogenesis of ethanol-induced birth defects. However, there is a fundamental gap in understanding how ethanol leads to apoptotic cell death in embryos. Sulforaphane (SFN) is a chemical that is abundant in broccoli sprouts. Compelling evidence indicates that SFN or SFN-rich broccoli sprouts trigger the induction of antioxidant enzymes through activation of Nrf2 signaling and prevent cancer and other diseases. It was recently discovered that SFN can regulate gene expression through epigenetic mechanisms. We have recently demonstrated that SFN can significantly diminish ethanol- induced apoptosis in neural crest cells (NCCs). Our long-term goal is directed toward the development of effective strategies against ethanol's teratogenesis; strategies based on prevention of ethanol-induced apoptosis through targeting specific pathways involved in apoptosis. The overall objective of this particular proposal is to elucidate the epigenetic mechanisms by which SFN epigenetically regulates the anti-apoptotic gene expression and prevent ethanol-induced apoptosis, and to develop a safe and effective regimen to diminish the incidence and severity of FASD using SFN, a safe “nutraceutical”. The central hypothesis of this project is that ethanol-induced epigenetic alterations lead to aberrant expression of the anti-apoptotic genes, resulting in excessive apoptosis and malformations in embryos, which can be prevented by epigenetic modulation elicited by SFN or SFN-rich broccoli sprout extract. Our hypothesis has been formulated on the basis of strong preliminary data produced in our laboratory. To test our hypothesis, the following specific aims will be addressed: Aim 1: To identify the anti-apoptotic genes that are epigenetically silenced by ethanol and derepressed by SNF in ethanol-exposed NCCs and mouse embryos. Aim 2: To elucidate the mechanisms by which SFN epigenetically modulates the expression of the anti-apoptotic genes and apoptosis in ethanol- exposed NCCs and mouse embryos. Aim 3: To test the hypothesis that epigenetic modulation of the anti- apoptotic genes by maternal dietary SFN-rich broccoli sprout extract (BSE) represents a novel therapeutic strategy for preventing ethanol-induced teratogenesis. The proposed work is innovative, because it focuses on a novel approach, epigenetic modulation of the anti-apoptotic genes, to preventing ethanol-induced teratogenesis. The theoretical concept described in the application is also highly innovative because this is the first study attempting to prevent FASD through the use of bioactive compounds derived from a vegetable. The results from this study will be significant, because they are expected to illustrate the potential of a practical nutraceutical-based therapeutic strategy for FASD.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Role of exosomes in the coordinated migration of neural crest cells and placodes and ethanol-induced teratogenesis
  • 批准号:
    10677038
  • 项目类别:
  • 资助金额:
    $35.21万
  • 财政年份:
    2020
  • 负责人:
    Shao-yu Chen
  • 依托单位:
Role of exosomes in the coordinated migration of neural crest cells and placodes and ethanol-induced teratogenesis
  • 批准号:
    10463617
  • 项目类别:
  • 资助金额:
    $35.21万
  • 财政年份:
    2020
  • 负责人:
    Shao-yu Chen
  • 依托单位:
Role of exosomes in the coordinated migration of neural crest cells and placodes and ethanol-induced teratogenesis
  • 批准号:
    10221505
  • 项目类别:
  • 资助金额:
    $35.11万
  • 财政年份:
    2020
  • 负责人:
    Shao-yu Chen
  • 依托单位:
Enhancer-mediated transcriptional dysregulation in neural crest cells and ethanol-induced teratogenesis
  • 批准号:
    10056415
  • 项目类别:
  • 资助金额:
    $25.83万
  • 财政年份:
    2016
  • 负责人:
    Shao-yu Chen
  • 依托单位:
海外基金