PMID- 26833042 OWN - NLM STAT- MEDLINE DCOM- 20170410 LR - 20211204 IS - 1615-2573 (Electronic) IS - 0910-8327 (Linking) VI - 31 IP - 10 DP - 2016 Oct TI - Repetitive restriction of muscle blood flow enhances mTOR signaling pathways in a rat model. PG - 1685-95 LID - 10.1007/s00380-016-0801-6 [doi] AB - 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. FAU - Nakajima, Toshiaki AU - Nakajima T AUID- ORCID: 0000-0001-9545-7529 AD - Department of Cardiovascular Medicine, Dokkyo Medical University and Heart Center, Dokkyo Medical University Hospital, 880 Kitakobayashi, Mibu, Tochigi, 321-0293, Japan. nakat@dokkyomed.ac.jp. FAU - Yasuda, Tomohiro AU - Yasuda T AD - Seirei Christopher University, Shizuoka, Japan. FAU - Koide, Seiichiro AU - Koide S AD - Department of Engineering Science, Bioscience and Technology Program, University of Electro-Communications, Tokyo, Japan. FAU - Yamasoba, Tatsuya AU - Yamasoba T AD - Department of Otolaryngology, University of Tokyo, Tokyo, Japan. FAU - Obi, Syotaro AU - Obi S AD - Department of Cardiovascular Medicine and Research Support Center, Dokkyo Medical Univerasity, Tochigi, Japan. FAU - Toyoda, Shigeru AU - Toyoda S AD - Department of Cardiovascular Medicine, Dokkyo Medical University and Heart Center, Dokkyo Medical University Hospital, 880 Kitakobayashi, Mibu, Tochigi, 321-0293, Japan. FAU - Sato, Yoshiaki AU - Sato Y AD - Department of Basic Sciences in Medicine, Kaatsu International University, Battaramulla, Sri Lanka. FAU - Inoue, Teruo AU - Inoue T AD - Department of Cardiovascular Medicine, Dokkyo Medical University and Heart Center, Dokkyo Medical University Hospital, 880 Kitakobayashi, Mibu, Tochigi, 321-0293, Japan. FAU - Kano, Yutaka AU - Kano Y AD - Department of Engineering Science, Bioscience and Technology Program, University of Electro-Communications, Tokyo, Japan. LA - eng PT - Journal Article DEP - 20160201 PL - Japan TA - Heart Vessels JT - Heart and vessels JID - 8511258 RN - 0 (RNA, Messenger) RN - 0 (Ribosomal Protein S6) RN - EC 2.7.1.1 (mTOR protein, rat) RN - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Animals MH - Hypoxia/*metabolism MH - Male MH - Muscle, Skeletal/*metabolism MH - Muscular Atrophy MH - Phosphorylation MH - RNA, Messenger/metabolism MH - Rats MH - Rats, Wistar MH - Ribosomal Protein S6/*metabolism MH - Ribosomal Protein S6 Kinases, 70-kDa/*metabolism MH - *Signal Transduction MH - TOR Serine-Threonine Kinases/*metabolism OTO - NOTNLM OT - Blood flow restriction OT - Hypoxia OT - Mammalian target of rapamycin (mTOR) OT - Microvascular pO2 OT - Muscle atrophy OT - Myostatin OT - Rat skeletal muscle OT - p70 S6-kinase EDAT- 2016/02/03 06:00 MHDA- 2017/04/11 06:00 CRDT- 2016/02/03 06:00 PHST- 2015/10/20 00:00 [received] PHST- 2016/01/15 00:00 [accepted] PHST- 2016/02/03 06:00 [entrez] PHST- 2016/02/03 06:00 [pubmed] PHST- 2017/04/11 06:00 [medline] AID - 10.1007/s00380-016-0801-6 [pii] AID - 10.1007/s00380-016-0801-6 [doi] PST - ppublish SO - Heart Vessels. 2016 Oct;31(10):1685-95. doi: 10.1007/s00380-016-0801-6. Epub 2016 Feb 1.