...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Pim-1 kinase antagonizes aspects of myocardial hypertrophy and compensation to pathological pressure overload
【24h】

Pim-1 kinase antagonizes aspects of myocardial hypertrophy and compensation to pathological pressure overload

机译：Pim-1激酶可拮抗心肌肥大和对病理性压力超负荷的补偿

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Pim-1 kinase exerts potent cardioprotective effects in the myocardium downstream of AKT, but the participation of Pim-1 in cardiac hypertrophy requires investigation. Cardiac-specific expression of Pim-1 (Pim-WT) or the dominant-negative mutant of Pim-1 (Pim-DN) in transgenic mice together with adenoviral-mediated over-expression of these Pim-1 constructs was used to delineate the role of Pim-1 in hypertrophy. Transgenic overexpression of Pim-1 protects mice from pressure-overload-induced hypertrophy relative to wild-type controls as evidenced by improved hemodynamic function, decreased apoptosis, increases in antihypertrophic proteins, smaller myocyte size, and inhibition of hypertrophic signaling after challenge. Similarly, Pim-1 overexpression in neonatal rat cardio-myocyte cultures inhibits hypertrophy induced by endothelin-1. On the cellular level, hearts of Pim-WT mice show enhanced incorporation of BrdU into myocytes and a hypercellular phenotype compared to wild-type controls after hypertrophic challenge. In comparison, transgenic overexpression of Pim-DN leads to dilated cardiomyopathy characterized by increased apoptosis, fibrosis, and severely depressed cardiac function. Furthermore, overexpression of Pim-DN leads to reduced contractility as evidenced by reduced Ca~(2+) transient amplitude and decreased percentage of cell shortening in isolated myocytes. These data support a pivotal role for Pim-1 in modulation of hypertrophy by impacting responses on molecular, cellular, and organ levels.
机译：Pim-1激酶在AKT下游的心肌中发挥强大的心脏保护作用，但Pim-1参与心肌肥大的研究尚需进一步研究。 Pim-1（Pim-WT）或Pim-1的显性负突变体（Pim-DN）在转基因小鼠中的心脏特异性表达以及这些Pim-1构建体的腺病毒介导的过表达被用来描述Pim-1在肥大中的作用相对于野生型对照，Pim-1的转基因过表达可以保护小鼠免受压力超负荷引起的肥大，改善的血流动力学功能，减少的细胞凋亡，抗肥大蛋白的增加，心肌细胞的大小以及攻击后抑制肥大信号的作用证明了这一点。同样，新生大鼠心肌细胞培养物中的Pim-1过表达抑制了内皮素1诱导的肥大。在细胞水平上，与肥大性攻击后的野生型对照相比，Pim​​-WT小鼠的心脏显示BrdU掺入心肌细胞的增强，并且具有高细胞表型。相比之下，Pim-DN的转基因过表达导致扩张型心肌病，其特征是凋亡增加，纤维化和严重的心脏功能下降。此外，Pim-DN的过表达导致收缩力降低，这可通过减少Ca〜（2+）瞬时幅度和减少分离的心肌细胞中细胞缩短的百分比来证明。这些数据通过影响分子，细胞和器官水平的反应，支持Pim-1在肥大调节中的关键作用。

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