• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Cachexia, Sarcopenia and Muscle >Degenerin channel activation causes caspase-mediated protein degradation and mitochondrial dysfunction in adult C. elegans muscle
【24h】

Degenerin channel activation causes caspase-mediated protein degradation and mitochondrial dysfunction in adult C. elegans muscle

机译：简并蛋白通道激活导致成年线虫肌肉中胱天蛋白酶介导的蛋白质降解和线粒体功能障碍

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

摘要

Abstract Background Declines in skeletal muscle structure and function are found in various clinical populations, but the intramuscular proteolytic pathways that govern declines in these individuals remain relatively poorly understood. The nematode Caenorhabditis elegans has been developed into a model for identifying and understanding these pathways. Recently, it was reported that UNC-105/degenerin channel activation produced muscle protein degradation via an unknown mechanism. Methods Generation of transgenic and double mutant C . elegans , RNAi, and drug treatments were utilized to assess molecular events governing protein degradation. Western blots were used to measure protein content. Cationic dyes and adenosine triphosphate (ATP) production assays were utilized to measure mitochondrial function. Results unc-105 gain-of-function mutants display aberrant muscle protein degradation and a movement defect; both are reduced in intragenic revertants and in let-2 mutants that gate the hyperactive UNC-105 channel. Degradation is not suppressed by interventions suppressing proteasome-mediated, autophagy-mediated, or calpain-mediated degradation nor by suppressors of degenerin-induced neurodegeneration. Protein degradation, but not the movement defect, is decreased by treatment with caspase inhibitors or RNAi against ced-3 or ced-4 . Adult unc-105 muscles display a time-dependent fragmentation of the mitochondrial reticulum that is associated with impaired mitochondrial membrane potential and that correlates with decreased rates of maximal ATP production. Reduced levels of CED-4, which is sufficient to activate CED-3 in vitro , are observed in unc-105 mitochondrial isolations. Conclusions Constitutive cationic influx into muscle appears to cause caspase degradation of cytosolic proteins as the result of mitochondrial dysfunction, which may be relevant to ageing and sarcopenia.
机译：摘要背景在各种临床人群中发现骨骼肌结构和功能的下降，但控制这些个体下降的肌内蛋白水解途径仍然知之甚少。线虫秀丽隐杆线虫已经发展成为用于识别和理解这些途径的模型。最近，据报道，UNC-105 /去氢肾上腺素通道的激活通过未知机制导致肌肉蛋白降解。方法产生转基因和双突变C。线虫，RNAi和药物处理被用来评估控制蛋白质降解的分子事件。蛋白质印迹用于测量蛋白质含量。阳离子染料和三磷酸腺苷（ATP）的生产测定法用于测量线粒体功能。结果unc-105功能获得型突变体显示出异常的肌肉蛋白降解和运动缺陷。两者均在基因内回复子和控制hyperactive UNC-105通道的let-2突变体中减少。抑制蛋白酶体介导的，自噬介导的或钙蛋白酶介导的降解的干预措施，或简并蛋白诱导的神经变性的抑制剂均不能抑制降解。通过用胱天蛋白酶抑制剂或针对ced-3或ced-4的RNAi处理，可以减少蛋白质降解，但不能降低运动缺陷。成人unc-105肌肉显示线粒体网状结构随时间变化的碎片，与线粒体膜电位受损有关，并且与最大ATP产生速率降低相关。在unc-105线粒体分离物中观察到CED-4水平降低，足以在体外激活CED-3。结论阳离子性流入肌肉似乎是由于线粒体功能障碍导致胞浆蛋白半胱天冬酶降解的原因，可能与衰老和肌肉减少有关。

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