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01-10-2016 | Original Article

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

Authors: Toshiaki Nakajima, Tomohiro Yasuda, Seiichiro Koide, Tatsuya Yamasoba, Syotaro Obi, Shigeru Toyoda, Yoshiaki Sato, Teruo Inoue, Yutaka Kano

Published in: Heart and Vessels | Issue 10/2016

Abstract

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 (PmvO₂), 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, PmvO₂ 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, PmvO₂ 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 PmvO₂, 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.

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Title: Repetitive restriction of muscle blood flow enhances mTOR signaling pathways in a rat model
Authors: Toshiaki Nakajima
Tomohiro Yasuda
Seiichiro Koide
Tatsuya Yamasoba
Syotaro Obi
Shigeru Toyoda
Yoshiaki Sato
Teruo Inoue
Yutaka Kano
Publication date: 01-10-2016
Publisher: Springer Japan
Published in: Heart and Vessels / Issue 10/2016
Print ISSN: 0910-8327
Electronic ISSN: 1615-2573
DOI: https://doi.org/10.1007/s00380-016-0801-6

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