...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>FEBS Letters >Hypoxic regulation of the 6‐phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase gene family (PFKFB‐1–4) expression in vivo
【24h】

Hypoxic regulation of the 6‐phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase gene family (PFKFB‐1–4) expression in vivo

机译：体内对6-磷酸果糖-2-激酶/果糖-2,6-双磷酸酶基因家族（PFKFB-1-4）表达的低氧调节

获取原文
   

获取外文期刊封面封底 >>

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

摘要

>When oxygen becomes limiting, cells shift primarily to a glycolytic mode for generation of energy. A key regulator of glycolytic flux is fructose-2,6-bisphosphate (F-2,6-BP), a potent allosteric regulator of 6-phosphofructo-1-kinase (PFK-1). The levels of F-2,6-BP are maintained by a family of bifunctional enzymes, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB or PFK-2), which have both kinase and phosphatase activities. Each member of the enzyme family is characterized by their phosphatase:kinase activity ratio (K:B) and their tissue-specific expression. Previous work demonstrated that one of the PFK-2 isozyme genes, PFKFB-3, was induced by hypoxia through the hypoxia-inducible factor-1 (HIF-1) pathway. In this study we examined the basal and hypoxic expression of three members of this family in different organs of mice. Our findings indicate that all four isozymes (PFKFB-1–4) are responsive to hypoxia in vivo. However, their basal level of expression and hypoxia responsiveness varies in the different organs studied. Particularly, PFKFB-1 is highly expressed in liver, heart and skeletal muscle, with the highest response to hypoxia found in the testis. PFKFB-2 is mainly expressed in the lungs, brain and heart. However, the highest hypoxia responses are found only in liver and testis. PFKFB-3 has a variable low basal level of expression in all organs, except skeletal muscle, where it is highly expressed. Most importantly, its hypoxia responsiveness is the most ample of all three genes, being strongly induced in the lungs, liver, kidney, brain, heart and testis. Further studies showed that PFKFB-1 and PFKFB-2 were highly responsive to hypoxia mimics such as transition metals, iron chelators and inhibitors of HIF hydroxylases, suggesting that the hypoxia responsiveness of these genes is also regulated by HIF proteins. In summary, our data demonstrate that PFK-2 genes are responsive to hypoxia in vivo, indicating a physiological role in the adaptation of the organism to environmental or localized hypoxia/ischemia.
机译：>当氧气变得有限时，细胞主要转变为糖酵解模式以产生能量。糖酵解通量的关键调节剂是2,6-二磷酸果糖（F-2,6-BP），6-磷酸果糖-1-激酶（PFK-1）的有效变构调节剂。 F-2,6-BP的水平由一系列具有激酶和磷酸酶活性的双功能酶6-磷酸果糖-2-激酶/果糖-2,6-双磷酸酶（PFKFB或PFK-2）维持。该酶家族的每个成员都以其磷酸酶：激酶活性比（K：B）及其组织特异性表达为特征。先前的工作表明，PFK-2同工酶基因之一PFKFB-3是通过低氧诱导因子-1（HIF-1）途径被低氧诱导的。在这项研究中，我们检查了该家族三个成员在小鼠不同器官中的基础和低氧表达。我们的发现表明，体内所有四种同工酶（PFKFB-1–4）对缺氧都有反应。但是，它们的基础表达水平和缺氧反应性在所研究的不同器官中有所不同。特别是，PFKFB-1在肝脏，心脏和骨骼肌中高度表达，对睾丸中的缺氧反应最高。 PFKFB-2主要在肺，脑和心脏中表达。然而，仅在肝脏和睾丸中发现最高的缺氧反应。 PFKFB-3在除高表达的骨骼肌外的所有器官中都有可变的低基础表达水平。最重要的是，它的低氧反应性是这三个基因中最丰富的，在肺，肝，肾，脑，心脏和睾丸中被强烈诱导。进一步的研究表明，PFKFB-1和PFKFB-2对低氧模拟物（例如过渡金属，铁螯合剂和HIF羟化酶抑制剂）具有高响应性，表明这些基因的低氧响应性也受HIF蛋白调节。总而言之，我们的数据表明PFK-2基因在体内对缺氧有反应，表明该生物适应环境或局部缺氧/局部缺血的生理作用。

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