• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国卫生研究院文献>Blood >Hemostasis Thrombosis and Vascular Biology: Solenopsin the alkaloidal component of the fire ant (Solenopsis invicta) is a naturally occurring inhibitor of phosphatidylinositol-3-kinase signaling and angiogenesis
【2h】

Hemostasis Thrombosis and Vascular Biology: Solenopsin the alkaloidal component of the fire ant (Solenopsis invicta) is a naturally occurring inhibitor of phosphatidylinositol-3-kinase signaling and angiogenesis

机译：止血血栓形成和血管生物学：Solenopsin是火蚁（Solenopsis invicta）的生物碱成分是磷脂酰肌醇3激酶信号传导和血管生成的天然抑制剂。

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Phosphatidylinositol-3-kinase (PI3K), and its downstream effector Akt, or protein kinase Bα (PKBα), play a major regulatory role in control of apoptosis, proliferation, and angiogenesis. PI3K and Akt are amplified or overexpressed in a number of malignancies, including sarcomas, ovarian cancer, multiple myeloma, and melanoma. This pathway regulates production of the potent angiogenic factor vascular endothelial growth factor (VEGF), and protects tumor cells against both chemotherapy and reactive oxygen–induced apoptosis through phosphorylation of substrates such as apoptotic peptidase–activating factor-1 (APAF-1), forkhead proteins, and caspase 9. Given its diverse actions, compounds that suppress the PI3K/Akt pathway have potential pharmacologic utility as angiogenesis inhibitors and antineoplastic agents. Using the SVR angiogenesis assay, a screen of natural products, we isolated the alkaloid solenopsin, and found that it is a potent angiogenesis inhibitor. We also found that solenopsin inhibits the PI3K signaling pathway in cells upstream of PI3K, which may underlie its affects on angiogenesis. Consistent with inhibition of the activation of PI3K, solenopsin prevented the phosphorylation of Akt and the phosphorylation of its substrate forkhead box 01a (FOXO1a), a member of the forkhead family of transcription factors. Interestingly, solenopsin also inhibited Akt-1 activity in an ATP-competitive manner in vitro without affecting 27 of 28 other protein kinases tested.
机译：磷脂酰肌醇-3-激酶（PI3K）及其下游效应器Akt或蛋白激酶Bα（PKBα）在控制细胞凋亡，增殖和血管生成中起主要调节作用。 PI3K和Akt在许多恶性肿瘤中被扩增或过表达，包括肉瘤，卵巢癌，多发性骨髓瘤和黑色素瘤。该途径调节强大的血管生成因子血管内皮生长因子（VEGF）的产生，并通过诸如凋亡肽酶激活因子1（APAF-1）等底物的磷酸化保护肿瘤细胞免受化学疗法和活性氧诱导的细胞凋亡蛋白质和胱天蛋白酶9.鉴于其多种作用，抑制PI3K / Akt途径的化合物具有潜在的药理作用，可作为血管生成抑制剂和抗肿瘤药。使用SVR血管生成测定法（一种天然产物的筛选），我们分离了生物碱solenopsin，并发现它是有效的血管生成抑制剂。我们还发现，slenopsin抑制PI3K上游细胞中的PI3K信号传导途径，这可能是其对血管生成的影响的基础。与抑制PI3K的激活一致，slenopsin阻止了Akt的磷酸化及其底物叉头盒01a（FOXO1a）（叉头转录因子家族的成员）的磷酸化。有趣的是，slenopsin还可以在体外以ATP竞争性方式抑制Akt-1活性，而不会影响其他28种蛋白激酶中的27种。

著录项

相似文献

  • 外文文献
  • 中文文献
代理获取

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