The impact of mitokine MOTS-c administration on the soleus muscle of rats subjected to a 7-day hindlimb suspension.

IF 1.8 3区 生物学 Q4 CELL BIOLOGY
Daria A Sidorenko, Irina D Lvova, Sergey A Tyganov, Boris S Shenkman, Kristina A Sharlo
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引用次数: 0

Abstract

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.

线粒体分裂因子MOTS-c对后肢悬吊7天大鼠比目鱼肌的影响。
本研究旨在探讨MOTS-c对大鼠比目鱼肌在卸压7天后的主要功能改变——慢纤维向快纤维转化、萎缩和疲劳增加的影响。在雄性Wistar大鼠后肢卸甲7天期间,每天腹腔注射线粒体短肽MOTS-c。实验结束后,我们对比目鱼肌进行了离体疲劳测试,结果表明,在7天的后肢卸载过程中,给药MOTS-c可以防止疲劳增加。此外,通过免疫组织化学分析,我们发现MOTS-c可以阻止慢纤维向快纤维的转化,减轻比目鱼肌的慢肌萎缩纤维(但不是快纤维)。在MOTS-c组中,Akt和GSK3β磷酸化水平的下降被阻止,18s和28s rRNA水平维持在对照水平。与后肢卸载组相比,泛素连接酶MuRF和atrogin1 mRNA也有所降低。此外,MOTS-c还能阻止一些线粒体生物发生参数的表达和ACC磷酸化水平(AMPK靶点)的降低。因此,在后肢卸甲过程中注射MOTS-C导致几种蛋白质合成和降解过程的正常化,并支持确保肌肉抵抗疲劳的基因的表达。
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来源期刊
CiteScore
6.20
自引率
0.00%
发文量
21
审稿时长
>12 weeks
期刊介绍: The Journal of Muscle Research and Cell Motility has as its main aim the publication of original research which bears on either the excitation and contraction of muscle, the analysis of any one of the processes involved therein, the processes underlying contractility and motility of animal and plant cells, the toxicology and pharmacology related to contractility, or the formation, dynamics and turnover of contractile structures in muscle and non-muscle cells. Studies describing the impact of pathogenic mutations in genes encoding components of contractile structures in humans or animals are welcome, provided they offer mechanistic insight into the disease process or the underlying gene function. The policy of the Journal is to encourage any form of novel practical study whatever its specialist interest, as long as it falls within this broad field. Theoretical essays are welcome provided that they are concise and suggest practical ways in which they may be tested. Manuscripts reporting new mutations in known disease genes without validation and mechanistic insight will not be considered. It is the policy of the journal that cells lines, hybridomas and DNA clones should be made available by the developers to any qualified investigator. Submission of a manuscript for publication constitutes an agreement of the authors to abide by this principle.
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