Sidorenko Daria A, Lvova Irina D, Tyganov Sergey A, Shenkman Boris S, Sharlo Kristina A
Institute of Biomedical Problems, RAS, Moscow, Russia.
J Muscle Res Cell Motil. 2025 Jul 3. doi: 10.1007/s10974-025-09700-3.
The aim of the study was to investigate the effect of MOTS-c on the key functional alterations in the rat soleus muscle during 7-day unloading - the transformation of slow fibers into fast ones, atrophy and increased fatigue. We daily intraperitoneally injected male Wistar rats with a short mitochondrial peptide MOTS-c during 7-day unloading of their hind limbs. After the end of the experiment, we conducted an ex vivo fatigue test of soleus muscle and showed that the MOTS-c administration prevents increased fatigue during 7-day hind limb unloading. Also, using immunohistochemical analysis, we showed that MOTS-c prevents the transformation of slow fibers into fast ones, mitigates the slow muscle atrophy fibers (but not fast ones) of the soleus muscle. In the group receiving MOTS-c, the decrease in Akt and GSK3β phosphorylation was prevented, and the 18 S and 28 S rRNA levels were at the control level. The ubiquitin ligases MuRF and Atrogin-1 mRNA were also reduced compared to the hindlimb unloading group with placebo. In addition, MOTS-c prevented a decrease in the expression of a few mitochondrial biogenesis parameters and the level of ACC phosphorylation (AMPK target). Thus, the MOTS-C injections during hind limb unloading lead to the normalization of several protein synthesis and degradation processes and support the expression of genes that ensure muscle resistance to fatigue.
本研究的目的是探讨线粒体短肽MOTS-c对大鼠比目鱼肌在7天失重期间关键功能改变的影响，即慢肌纤维向快肌纤维的转变、萎缩和疲劳增加。在雄性Wistar大鼠后肢7天失重期间，我们每天腹腔注射短线粒体肽MOTS-c。实验结束后，我们对比目鱼肌进行了离体疲劳试验，结果表明，给予MOTS-c可防止后肢7天失重期间疲劳增加。此外，通过免疫组化分析，我们发现MOTS-c可防止慢肌纤维向快肌纤维的转变，减轻比目鱼肌慢肌纤维（而非快肌纤维）的萎缩。在接受MOTS-c的组中，Akt和GSK3β磷酸化的降低得到了预防，18S和28S rRNA水平处于对照水平。与给予安慰剂的后肢失重组相比，泛素连接酶MuRF和Atrogin-1的mRNA也有所降低。此外，MOTS-c可防止一些线粒体生物发生参数的表达下降以及ACC磷酸化（AMPK靶点）水平的下降。因此，后肢失重期间注射MOTS-C可使几种蛋白质合成和降解过程正常化，并支持确保肌肉抗疲劳能力的基因表达。
