...
首页> 外文期刊>Evidence-based complementary and alternative medicine: eCAM >Curcumin Downregulates Human GM3 Synthase (hST3Gal V) Gene Expression with Autophagy Induction in Human Colon Carcinoma HCT116 Cells
【24h】

Curcumin Downregulates Human GM3 Synthase (hST3Gal V) Gene Expression with Autophagy Induction in Human Colon Carcinoma HCT116 Cells

机译:姜黄素下调人GM3合成酶(HST3GAL V)基因表达,在人结肠癌HCT116细胞中的自噬诱导

获取原文
获取原文并翻译 | 示例
   

获取外文期刊封面封底 >>

       

摘要

Our recent report showed that curcumin, polyphenolic compound isolated from the herb Curcuma longa, upregulated the gene expression of human GD3 synthase (hST8Sia I) responsible for ganglioside GD3 synthesis with autophagy induction in human lung adenocarcinoma A549 cells. In this study, on the contrary to this finding, we demonstrated that curcumin downregulated the gene expression of human GM3 synthase (hST3Gal V) catalyzing ganglioside GM3 synthesis with autophagy induction in human colon carcinoma HCT116 cells. To clarify the mechanism leading to the downregulation of hST3Gal V gene expression in curcumin-treated HCT116 cells, we analyzed the curcumin-inducible promoter of the hST3Gal V gene by luciferase reporter assays. Promoter deletion analysis demonstrated that the -177 to -83 region, which includes putative binding sites for transcription factors NFY, CREB/ATF, SP1, EGR3, and MZF1, acts as the curcumin-responsive promoter of the hST3Gal V gene. Site-directed mutagenesis and chromatin immunoprecipitation analysis demonstrated that the CREB/ATF binding site at -143 is pivotal for curcumin-induced downregulation of hST3Gal V gene in HCT116 cells. The transcriptional activation of hST3Gal V in HCT116 cells was significantly repressed by an inhibitor of AMP-activated protein kinase (AMPK). These results suggest that AMPK signal pathway mediates hST3Gal V gene expression in HCT116 cells.
机译:我们最近的报告显示,姜黄素,从草本植物莪术中分离的多酚化合物,上调了人GD3合成酶(HST8SIA I)的基因表达,其负责神经节苷脂GD3合成的人肺腺癌A549细胞的自噬诱导。在这项研究中,与此发现相反,我们证明姜黄素下调了人GM3合酶(HST3GAL V)催化神经酰基合成的基因表达与人结肠癌HCT116细胞中的自噬诱导。为了阐明姜黄素处理的HCT116细胞中HST3GAL V基因表达的下调的机制,通过荧光素酶报告分析分析了HST3GAL V基因的姜黄素诱导促进剂。启动子缺失分析证明-177至-83区,包括用于转录因子NFY,CREB ​​/ ATF,SP1,EGR3和MZF1的推定结合位点,作为HST3GALV基因的姜黄素响应促进剂。定向诱变和染色质免疫沉淀分析证明-143的CREB ​​/ ATF结合位点是姜黄素诱导的HCT116细胞中HST3GAL V基因下调的焦点。通过AMP活化蛋白激酶(AMPK)的抑制剂,HCT1116细胞中HST3GAL V的转录激活显着压制。这些结果表明AMPK信号途径在HCT116细胞中介导HST3GAL v基因表达。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号