...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cellular Signalling >Nerve growth factor stimulation of ERK1/2 phosphorylation requires both p75 ~(NTR)and α9β1 integrin and confers myoprotection towards ischemia in C2C12 skeletal muscle cell model
【24h】

Nerve growth factor stimulation of ERK1/2 phosphorylation requires both p75 ~(NTR)and α9β1 integrin and confers myoprotection towards ischemia in C2C12 skeletal muscle cell model

机译：神经生长因子刺激ERK1 / 2磷酸化需要p75〜（NTR）和α9β1整联蛋白，并在C2C12骨骼肌细胞模型中赋予对缺血的心肌保护

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

The functions of nerve growth factor(NGF)in skeletal muscles physiology and pathology are not clear and call for an updated investigation. To achieve this goal we sought to investigate NGF-induced ERK1/2 phosphorylation and its role in the C2C12 skeletal muscle myoblasts and myotubes. RT-PCR and western blotting experiments demonstrated expression of p75 ~(NTR), α9β1 integrin, and its regulator ADAM12, but not trkA in the cells, as also found in gastrocnemius and quadriceps mice muscles. Both proNGF and βNGF induced ERK1/2 phosphorylation, a process blocked by(a)the specific MEK inhibitor, PD98059;(b)VLO5, a MLD-disintegrin with relative selectivity towards α9β1 integrin; and(c)p75 ~(NTR)antagonists Thx-B and LM-24, but not the inactive control molecule backbone Thx. Upon treatment for 4days with either anti-NGF antibody or VLO5 or Thx-B, the proliferation of myoblasts was decreased by 60-70%, 85-90% and 60-80% respectively, indicative of trophic effect of NGF which was autocrinically released by the cells. Exposure of myotubes to ischemic insult in the presence of βNGF, added either 1h before oxygen-glucose-deprivation or concomitant with reoxygenation insults, resulted with about 20% and 33% myoprotection, an effect antagonized by VLO5 and Thx-B, further supporting the trophic role of NGF in C2C12 cells. Cumulatively, the present findings propose that proNGF and βNGF-induced ERK1/2 phosphorylation in C2C12 cells by functional cooperation between p75 ~(NTR)and α9β1 integrin, which are involved in myoprotective effects of autocrine released NGF. Furthermore, the present study establishes an important trophic role of α9β1 in NGF-induced signaling in skeletal muscle model, resembling the role of trkA in neurons. Future molecular characterization of the interactions between NGF receptors in the skeletal muscle will contribute to the understanding of NGF mechanism of action and may provide novel therapeutic targets.
机译：神经生长因子（NGF）在骨骼肌生理和病理中的功能尚不清楚，需要进行更新的研究。为实现此目标，我们试图研究NGF诱导的ERK1 / 2磷酸化及其在C2C12骨骼肌成肌细胞和肌管中的作用。 RT-PCR和蛋白质印迹实验证明p75〜（NTR），α9β1整联蛋白及其调节剂ADAM12的表达，但在腓肠肌和股四头肌的肌肉中却没有表达trkA。 proNGF和βNGF均诱导ERK1 / 2磷酸化，这一过程被（a）特异性MEK抑制剂PD98059;（b）VLO5（一种对α9β1整联蛋白具有相对选择性的MLD-整联蛋白）阻断; （c）p75〜（NTR）拮抗剂Thx-B和LM-24，而不是无活性的控制分子骨架Thx。用抗NGF抗体或VLO5或Thx-B处理4天后，成肌细胞的增殖分别降低了60-70％，85-90％和60-80％，这表明NGF的营养作用已被自体释放由细胞。在存在缺氧葡萄糖剥夺前1小时或伴有复氧损伤的情况下，在存在βNGF的情况下将肌管暴露于缺血性损伤，可产生约20％和33％的心肌保护作用，这种作用被VLO5和Thx-B拮抗，进一步支持了NGF在C2C12细胞中的营养作用。累积地，本发明人发现，通过p75〜（NTR）和α9β1整联蛋白之间的功能合作，proNGF和βNGF诱导的C2C12细胞中ERK1 / 2磷酸化参与了自分泌释放的NGF的心肌保护作用。此外，本研究建立了α9β1在骨骼肌模型中NGF诱导的信号传导中的重要营养作用，类似于trkA在神经元中的作用。骨骼肌中NGF受体之间相互作用的未来分子表征将有助于对NGF作用机理的理解，并可能提供新的治疗靶标。

著录项

相似文献

  • 外文文献
  • 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