基础医学与临床 ›› 2011, Vol. 31 ›› Issue (9): 959-964.

• 研究论文 •    下一篇

姜黄素对心脏发育相关基因表达的影响及其表观遗传调控机制

孙慧超1,吕铁伟2,朱静1,黄国英3,田杰1,吴晓云4   

  1. 1. 重庆医科大学附属儿童医院
    2. 重庆医科大学儿童医院心血管内科
    3. 复旦大学附属儿童医院心血管内科
    4. 重庆医科大学附属儿童医院心内科
  • 收稿日期:2010-10-11 修回日期:2010-11-10 出版日期:2011-09-05 发布日期:2011-09-05
  • 通讯作者: 田杰 E-mail:jietian@cqmu.edu.cn
  • 基金资助:
    国家自然科学基金;973国家重点基础研究发展规划项目

Effects of curcumin on heart development-related genes expression and the associated epigenetic mechanism

  • Received:2010-10-11 Revised:2010-11-10 Online:2011-09-05 Published:2011-09-05
  • Contact: Jie TIAN E-mail:jietian@cqmu.edu.cn

摘要: 目的 阐明姜黄素(Curcumin)对心脏发育相关基因GATA4,MEF2C和Nkx2.5表达的影响,并探讨其表观调控机制。方法 姜黄素处理新生鼠心肌细胞后,分别用ELISA,western blot,real time RT-PCT和染色质免疫沉淀(chromatin immunoprecipitation, ChIP)检测组蛋白乙酰化酶活性,组蛋白H3乙酰化修饰状态,GATA4,MEF2C和Nkx2.5的表达和启动子区域组蛋白乙酰化水平。结果 30mol/L姜黄素作用24小时能有效降低心肌细胞中组蛋白乙酰化酶活性和组蛋白H3的乙酰化修饰状态,GATA4,MEF2C和Nkx2.5的表达水平明显降低(P<0.05),ChIP-PCR结果证实基因启动子区域组蛋白乙酰化修饰水平明显降低(P<0.05)。结论 启动子区域组蛋白乙酰化修饰状态降低导致染色质构型紧密,可能为姜黄素抑制GATA4,MEF2C和Nkx2.5表达的调控机制之一。

关键词: 组蛋白乙酰化, 姜黄素, p300, 表观遗传学, 心肌细胞

Abstract: Objective To investigate the effects of curcumin on heart development-related genes GATA4, MEF2C and Nkx2.5, and to explore the epigenetic regulation mechanism. Methods Neonatal mouse cardiocytes were treated with curcumin with different concentration and different time. ELISA was used to detect the histone acetylase (HATs) activity of cardiocytes, western blot to detect the acetylation of histone H3, real time RT-PCT to measure the expression of heart development-related genes GATA4, MEF2C and Nkx2.5, and chromatin immunoprecipitation (ChIP)-PCR to analyse the chromatin struction. Results 30mol/L of curcumin could inhibit the HAT activity and the acetylation of histone H3 at 24 hours. Accordingly the expression of GATA4, MEF2C and Nkx2.5 were repressed significantly (P<0.05). The result of ChIP-PCR showed that the the acetylation of histone which bound with promoter regions of these genes were reduced. Conclusion Curcumin could inhibit the HAT activity and repress the expression of heart development-related genes GATA4, MEF2C and Nkx2.5 effectively. And the loose structure of chromatin induced by hypoacetylation of histone bound with promoter regions might be one mechanism of this effect.

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