Repetitive restriction of muscle blood flow enhances mTOR signaling pathways in a rat model

• Published in: Heart and vessels Vol. 31; no. 10; pp. 1685 - 1695
• Main Authors: Nakajima, Toshiaki, Yasuda, Tomohiro, Koide, Seiichiro, Yamasoba, Tatsuya, Obi, Syotaro, Toyoda, Shigeru, Sato, Yoshiaki, Inoue, Teruo, Kano, Yutaka
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.10.2016; Springer Nature B.V
• Subjects: Animals; Biomedical Engineering and Bioengineering; Cardiac Surgery; Cardiology; Hypoxia; Hypoxia - metabolism; Male; Medicine; Medicine & Public Health; Muscle, Skeletal - metabolism; Muscular Atrophy; Musculoskeletal system; Original Article; Phosphorylation; Protein expression; Rats; Rats, Wistar; Ribosomal Protein S6 - metabolism; Ribosomal Protein S6 Kinases, 70-kDa - metabolism; RNA, Messenger - metabolism; Rodents; Signal Transduction; TOR Serine-Threonine Kinases - metabolism; Vascular Surgery; Blood flow restriction; p70 S6-kinase; Mammalian target of rapamycin (mTOR); Muscle atrophy; Myostatin; Hypoxia; Microvascular pO; Rat skeletal muscle; Microvascular pO2
• ISSN: 0910-8327; 1615-2573
• DOI: 10.1007/s00380-016-0801-6

Skeletal muscle is a plastic organ that adapts its mass to various stresses by affecting pathways that regulate protein synthesis and degradation. This study investigated the effects of repetitive restriction of muscle blood flow (RRMBF) on microvascular oxygen pressure (PmvO 2 ), mammalian target of rapamycin (mTOR) signaling pathways, and transcripts associated with proteolysis in rat skeletal muscle. Eleven-week-old male Wistar rats under anesthesia underwent six RRMBF consisting of an external compressive force of 100 mmHg for 5 min applied to the proximal portion of the right thigh, each followed by 3 min rest. During RRMBF, PmvO 2 was measured by phosphorescence quenching techniques. The total RNA and protein of the tibialis anterior muscle were obtained from control rats, and rats treated with RRMBF 0–6 h after the stimuli. The protein expression and phosphorylation of various signaling proteins were determined by western blotting. The mRNA expression level was measured by real-time RT-PCR analysis. The total muscle weight increased in rats 0 h after RRMBF, but not in rats 1–6 h. During RRMBF, PmvO 2 significantly decreased (36.1 ± 5.7 to 5.9 ± 1.7 torr), and recovered at rest period. RRMBF significantly increased phosphorylation of p70 S6-kinase (p70S6k), a downstream target of mTOR, and ribosomal protein S6 1 h after the stimuli. The protein level of REDD1 and phosphorylation of AMPK and MAPKs did not change. The mRNA expression levels of FOXO3a, MuRF-1, and myostatin were not significantly altered. These results suggested that RRMBF significantly decreased PmvO 2 , and enhanced mTOR signaling pathways in skeletal muscle using a rat model, which may play a role in diminishing muscle atrophy under various conditions in human studies.