Myology Laboratory, Institute of Biomedical Problems, RAS, Moscow, Russia.
Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine-Northwest, Gary, IN, USA.
Arch Biochem Biophys. 2022 Aug 15;725:109291. doi: 10.1016/j.abb.2022.109291. Epub 2022 May 18.
Skeletal muscle unloading leads to the decreased electrical activity and decline of muscle tone.
Current study evaluated the effect of muscle tone preservation achieved by tetanus toxin (TeNT) treatment on signaling pathways regulating atrophic processes during unloading.
Four groups of rats were used: non-treated control (C), control rats with TeNT administration (CT), 7 days of unloading/hindlimb suspension with placebo (HS), and 7 days of unloading with TeNT administration (HST).
Absolute and relative force of tetanic contractions was decreased by 65% in soleus muscle of HS rats when compared with C. Treatment with TeNT significantly lessened force decline in soleus muscle of HST rats when compared with HS. TeNT administration increased myosin heavy chain I beta (MyHC Iβ) expression in CT rats and prevented MyHC Iβ loss in HST group when compared with C rats. Desmin content was lower by 31.4% (p < 0.05) in HS group when compared with HST. Calpain-1 expression was increased in HS group when compared with C, CT and HST. There was a decrease in p-p70S6K content (41%, p < 0,05) and an increase in p-eEF2 content (77%, p < 0,05) in HS group when compared with C, while there were no significant differences in the content of these proteins between HST, CT and C groups.
Treatment with TeNT significantly diminished unloading-induced decline of soleus muscle mass and mechanical properties and affected the regulation of MyHC Iβ expression. These effects are mediated by signaling pathways regulating protein synthesis and degradation.
骨骼肌卸载会导致电活动减少和肌肉张力下降。
本研究评估了通过破伤风毒素（TeNT）治疗保持肌肉张力对卸载过程中调节萎缩过程的信号通路的影响。
使用四组大鼠：未经处理的对照组（C）、给予 TeNT 的对照组（CT）、接受 7 天的卸载/后肢悬吊（HS）和接受 7 天的卸载和 TeNT 治疗（HST）。
与 C 组相比，HS 组大鼠比目鱼肌的强直收缩力绝对值和相对值下降了 65%。与 HS 组相比，HST 组大鼠比目鱼肌的 TeNT 治疗显著减轻了力的下降。TeNT 治疗增加了 CT 大鼠的肌球蛋白重链 Iβ（MyHC Iβ）表达，并防止了 HST 组大鼠的 MyHC Iβ 丢失，与 C 组大鼠相比。HS 组的结蛋白含量降低了 31.4%（p<0.05）。与 C、CT 和 HST 组相比，HS 组的钙蛋白酶-1 表达增加。与 C 组相比，HS 组的 p-p70S6K 含量下降了 41%（p<0.05），p-eEF2 含量增加了 77%（p<0.05），而 HST、CT 和 C 组之间这些蛋白质的含量没有显著差异。
TeNT 治疗显著减轻了卸载引起的比目鱼肌质量和机械性能下降，并影响了 MyHC Iβ 表达的调节。这些作用是通过调节蛋白质合成和降解的信号通路介导的。
