• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>American Journal of Physiology >Clenbuterol suppresses proteasomal and lysosomal proteolysis and atrophy-related genes in denervated rat soleus muscles independently of Akt
【24h】

Clenbuterol suppresses proteasomal and lysosomal proteolysis and atrophy-related genes in denervated rat soleus muscles independently of Akt

机译：盐酸克仑特罗独立于Akt抑制失神经大鼠比目鱼肌中的蛋白酶体和溶酶体蛋白水解及萎缩相关基因

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

Although it is well known that administration of the selective β 2-adrenergic agonist clenbuterol (CB) protects muscle following denervation (DEN), the underlying molecular mechanism remains unclear. We report that in vivo treatment with CB (3 mg/kg sc) for 3 days induces antiproteolytic effects in normal and denervated rat soleus muscle via distinct mechanisms. In normal soleus muscle, CB treatment stimulates protein synthesis, inhibits Ca 2+-dependent proteolysis, and increases the levels of calpastatin protein. On the other hand, the administration of CB to DEN rats ameliorates the loss of muscle mass, enhances the rate of protein synthesis, attenuates hyperactivation of proteasomal and lysosomal proteolysis, and suppresses the transcription of the lysosomal protease cathepsin L and of atrogin-1/MAFbx and MuRF1, two ubiquitin (Ub) ligases involved in muscle atrophy. These effects were not associated with alterations in either IGF-I content or Akt phosphorylation levels. In isolated muscles, CB (10 -6 M) treatment significantly attenuated DEN-induced overall proteolysis and upregulation in the mRNA levels of the Ub ligases. Similar responses were observed in denervated muscles exposed to 6-BNZ-cAMP (500 μM), a PKA activator. The in vitro addition of triciribine (10 μM), a selective Akt inhibitor, did not block the inhibitory effects of CB on proteolysis and Ub ligase mRNA levels. These data indicate that short-term treatment with CB mitigates DEN-induced atrophy of the soleus muscle through the stimulation of protein synthesis, downregulation of cathepsin L and Ub ligases, and consequent inhibition of lysosomal and proteasomal activities and that these effects are independent of Akt and possibly mediated by the cAMP/PKA signaling pathway.
机译：尽管众所周知，选择性β2-肾上腺素能激动剂克仑特罗（CB）的给药可以保护神经支配后的肌肉（DEN），但其潜在的分子机制仍不清楚。我们报道体内用CB（3 mg / kg sc）治疗3天通过不同的机制诱导正常和失神经大鼠比目鱼肌的抗蛋白水解作用。在正常的比目鱼肌中，CB治疗可刺激蛋白质合成，抑制Ca 2+依赖性蛋白水解，并增加钙蛋白酶抑制蛋白的水平。另一方面，向DEN大鼠施用CB可改善肌肉质量的丧失，提高蛋白质合成的速度，减弱蛋白酶体和溶酶体蛋白水解的过度活化，并抑制溶酶体蛋白酶组织蛋白酶L和atrogin-1 /的转录。 MAFbx和MuRF1，两种泛素（Ub）连接酶，参与肌肉萎缩。这些作用与IGF-1含量或Akt磷酸化水平的改变均无关。在离体的肌肉中，CB（10 -6 M）处理显着减弱了DEN诱导的整体蛋白水解和Ub连接酶mRNA水平的上调。在暴露于6-BNZ-cAMP（500μM）（一种PKA激活剂）的失神经肌肉中观察到了类似的反应。体外添加选择性Akt抑制剂Triciribine（10μM）不会阻止CB对蛋白水解和Ub连接酶mRNA水平的抑制作用。这些数据表明，CB的短期治疗可通过刺激蛋白质合成，下调组织蛋白酶L和Ub连接酶并因此抑制溶酶体和蛋白酶体活性来减轻DEN引起的比目鱼肌萎缩，并且这些作用与Akt无关并可能由cAMP / PKA信号通路介导。

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