Abstract 17477: Repetitive Restriction of Muscle Blood Flow Enhances mTOR Signaling Pathways in a Rat Model
Background: Skeletal muscle is a plastic organ that adapts its mass to various stresses by affecting pathways that regulate protein and cellular turnover . Skeletal muscle loss develops in patients with prolonged immobility and bed rest.This study investigated the effects of repetitive restriction of muscle blood flow (RRMBF) on microvascular pO2 (Pmvo2), mammalian target of rapamycin (mTOR) signaling pathways, and transcripts associated with proteolysis in rat skeletal muscle.
Method: Eleven-week-old male Wistar rats under anesthesia were subjected to six repetitions of muscle blood flow restriction consisting of 100 mmHg restriction 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 were obtained from control rats, and rats with RRMBF immediately after the stimuli (0 h), 1 h, 3 h, and 6 h. The protein expression and phosphorylation of signaling proteins were determined by western blotting. The real-time RT-PCR analysis was used to measure the expression level of mRNA.
Result: The total muscle weight was significantly increased in rats 0 h, but not in rats 1-6 h. During RRMBF, Pmvo2 significantly decreased, and gradually 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. RRMBF had increased HIF-1α protein at 1 h after RRMBF, compared with controls.
Conclusion: These results suggest that RRMBF enhances mTOR signaling pathways in skeletal muscle using a rat model, while it does not affect the ubiquitin/proteolysis pathway, REDD1 and AMPK phosphorylation. RRMBF may be a novel method for preventing muscle loss in bed rest patients and patients with disuse syndrome.
- © 2013 by American Heart Association, Inc.