Β-GPA administration activates slow oxidative muscle signaling pathways and protects soleus muscle against the increased fatigue under 7-days of rat hindlimb suspension

• Published in: Archives of biochemistry and biophysics 2023-07, Vol.743, p.109647-109647, Article 109647
• Main Authors: Sharlo, K.A., Lvova, I.D., Sidorenko, D.A., Tyganov, S.A., Sharlo, D.T., Shenkman, B.S.
• Format: Article
• Language: English
• Subjects: Animals; Hindlimb Suspension - physiology; Male; Muscle, Skeletal - metabolism; Muscular Atrophy - metabolism; Oxidative Stress; Rats; Rats, Wistar; Signal Transduction
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2023.109647

Unloading of slow-twitch muscles results in increased muscle fatigue and the mechanisms of this effect are poorly studied. We aimed to analyze the role of high-energy phosphates accumulation during the first week of rat hindlimb suspension plays in a fiber-type phenotype shift towards fast-type fatigable muscle fibers. Male Wistar rats were divided into 3 groups (n = 8): C - vivarium control; 7HS - 7-day hindlimb suspension; 7HB - 7-day hindlimb suspension with intraperitoneal injection of beta-guanidine propionic acid (β-GPA, 400 mg/kg b w). β‐GPA is a competitive inhibitor of creatine kinase and it reduces concentrations of ATP and phosphocreatine. In the 7HB group, β-GPA treatment protected a slow-type signaling network in an unloaded soleus muscle, including MOTS-C, AMPK, PGC1 α and micro-RNA-499. These signaling effects resulted in a preserved soleus muscle fatigue resistance, slow-type muscle fibers percentage and mitochondrial DNA copy number under muscle unloading. [Display omitted] •Unloading leads to increased muscleweakness.•Male rats were treated with beta-GPA during 7 -days of unloading.•beta-GPA prevented the unloading-induced muscle fatigue.