• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>ACS Omega >AICAR Stimulates the Pluripotency Transcriptional Complex in Embryonic Stem Cells Mediated by PI3K, GSK3β, and β-Catenin
【24h】

AICAR Stimulates the Pluripotency Transcriptional Complex in Embryonic Stem Cells Mediated by PI3K, GSK3β, and β-Catenin

机译：AICAR刺激由PI3K，GSK3β和β-catenin介导的胚胎干细胞中的多能转录复合物

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Pluripotent stem cells maintain the property of self-renewal and differentiate into all cell types under clear environments. Though the gene regulatory mechanism for pluripotency has been investigated in recent years, it is still not completely understood. Here, we show several signaling pathways involved in the maintenance of pluripotency. To investigate whether AMPK is involved in maintaining the pluripotency in mouse embryonic stem cells (mESCs) and elucidating the possible molecular mechanisms, implicated D3 and R1/E mESC lines were used in this study. Cells were cultured in the absence or presence of LIF and treated with 1 mM and 0.5 mM 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR), 2 mM metformin, compound C, and the PI3K inhibitor LY294002 for 24, 72, and 120 h. The levels of Nanog, Oct3/4, and REX1 and Brachyury, Notch2, and Gata4 mRNAs and Nanog or OCT3/4 protein levels were analyzed. Alkaline phosphatase and the cellular cycle were determined. The pGSK3β, GSK3β, p-β-catenin, and β-catenin protein levels were also investigated. We found that AMPK activators such as AICAR and metformin increase mRNA expression of pluripotency markers and decrease mRNA expression of differentiation markers in R1/E and D3 ES cells. AICAR increases phosphatase activity and arrests the cellular cycle in the G1 phase in these cells. We describe that AICAR effects were mediated by AMPK activation using a chemical inhibitor or by silencing this gene. AICAR effects were also mediated by PI3K, GSK3β, and β-catenin in R1/E ES cells. According to our findings, we provide a mechanism by which AICAR increases and maintains a pluripotency state through enhanced Nanog expression, involving AMPK/PI3K and p-GSK3β Ser21/9 pathways backing up the AICAR function as a potential target for this drug controlling pluripotency. The highlights of this study are that AICAR (5-aminoimidazole-4-carboxamied-1-b-riboside), an AMP protein kinase (AMPK) activator, blocks the ESC differentiation and AMPK is a key enzyme for pluripotency and shows valuable data to clarify the molecular pluripotency mechanism.
机译：多能干细胞维持自我更新的性质，并在透明环境下区分所有细胞类型。虽然近年来已经调查了多能性的基因调节机制，但它仍然没有完全理解。在这里，我们展示了多能性维持的几种信令途径。为了研究AMPK是否参与维持小鼠胚胎干细胞（MESCS）中的多能性并阐明可能的分子机制，本研究中使用了牵连的D3和R1 / E MESC线。在LiF的情况下培养细胞并用1mM和0.5mM 5-氨基咪唑-4-甲酰胺-1-β-D-核苷酸（AICAR），2mM二甲双胍，化合物C和PI3K抑制剂Ly294002处理24,72和120小时。分析了纳米，Oct3 / 4和REX1和BRACHYURY，NOTCH2和GATA4 MRNA和NANOG或OCT3 / 4蛋白水平的水平。确定碱性磷酸酶和细胞周期。还研究了PGSK3β，GSK3β，P-β-Catenin和β-连环蛋白蛋白水平。我们发现AMPK激活剂如AICAR和二甲双胍增加了多能性标记的mRNA表达，并降低R1 / E和D3 ES细胞中分化标志物的mRNA表达。 AICAR增加了磷酸酶活性并在这些细胞中捕获G1相中的细胞周期。我们描述了通过使用化学抑制剂或通过沉默这种基因的AMPK活化介导的AICAR效应。 AICAR效应也由PI3K，GSK3β和β-Catenin介导的R1 / E ES细胞介导。根据我们的发现，我们提供了一种机制，通过增强纳米表达，AICAR增加并维持多能性状态，涉及AMPK / PI3K和P-GSK3βSER21/ 9载体作为该药物控制多能性的潜在靶标。本研究的亮点是AICAR（5-氨基咪唑-4-羧酰胺-1-B-核糖苷），AMP蛋白激酶（AMPK）活化剂，ESC分化和AMPK是多能性的关键酶，并显示有价值的数据澄清分子多能性机制。

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