Comprehensive Research Institutes, Waseda University, Saitama, Japan.
Biochem Biophys Res Commun. 2010 Mar 26;394(1):136-40. doi: 10.1016/j.bbrc.2010.02.130. Epub 2010 Feb 23.
This study investigated regulation of autophagy in slow-twitch soleus and fast-twitch plantaris muscles in fasting-related atrophy. Male Fischer-344 rats were subjected to fasting for 1, 2, or 3 days. Greater weight loss was observed in plantaris muscle than in soleus muscle in response to fasting. Western blot analysis demonstrated that LC3-II, a marker protein for macroautophagy, was expressed at a notably higher level in plantaris than in soleus muscle, and that the expression level was fasting duration-dependent. To identify factors related to LC3-II enhancement, autophagy-related signals were examined in both types of muscle. Phosphorylated mTOR was reduced in plantaris but not in soleus muscle. FOXO3a and ER stress signals were unchanged in both muscle types during fasting. These findings suggest that preferential atrophy of fast-twitch muscle is associated with induction of autophagy during fasting and that differences in autophagy regulation are attributable to differential signal regulation in soleus and plantaris muscle.
本研究探讨了自噬在与饥饿相关的萎缩的慢肌比目鱼肌和快肌跖肌中的调节作用。雄性 Fischer-344 大鼠接受禁食 1、2 或 3 天。与禁食相关的体重减轻在跖肌中比在比目鱼肌中更为明显。Western blot 分析表明,LC3-II,一种用于巨自噬的标记蛋白,在跖肌中比在比目鱼肌中表达水平更高,并且表达水平与禁食时间有关。为了鉴定与 LC3-II 增强相关的因素,在两种类型的肌肉中检查了与自噬相关的信号。磷酸化 mTOR 在跖肌中减少,但在比目鱼肌中没有减少。在禁食期间,FOXO3a 和 ER 应激信号在两种肌肉类型中均无变化。这些发现表明,在禁食期间,快肌的优先萎缩与自噬的诱导有关,而自噬调节的差异归因于比目鱼肌和跖肌中信号调节的差异。