Redox Regulation of Satellite Cells and Skeletal Muscle Healing

The Effect of Redox Potential on the Regulation of Satellite Cells and Skeletal Muscle Healing Following Exercise-Induced Muscle Damage

Skeletal muscle stem cells (Satellite cells) are indispensable for muscle growth and remodeling following myofibril damage. Skeletal muscle trauma is present in numerous catabolic conditions, characterized by elevated proteolysis and muscle wasting such as, cancer cachexia and muscular dystrophy, which result in physical capacity impairment and a deteriorated quality of life. Recent studies performed in animals and cell cultures indicate that the increased levels of inflammation and oxidative stress and the reduction of antioxidant defense may blunt the satellite cells response and myogenic programming during muscle healing. However, evidence regarding the effects of redox status on satellite cells and muscle myogenic potential in humans is lacking. Exercise-induced muscle damage bears striking similarities with the aforementioned conditions, which makes it a valuable tool to investigate the redox-dependent regulation of satellite cells during muscle healing. Thus, the objectives of the present study are to examine the effects of redox status perturbation (via N-acetylcysteine administration) on intracellular pathways responsible for satellite cells responses at rest and following aseptic muscle trauma induced by damaging exercise.

A total number of 40-60 young males aged 18-30 will be initially enrolled in the study. Then, participants will be allocated to either a 1) Low glutathione (GSH-low) or a 2) High glutathione (GSH-high) group based on the basal glutathione levels of their vastus lateralis muscle. In a double-blind, crossover, repeated measures design, participants will consume either Placebo (PLA) or N-acetylcysteine (NAC) before (7-day loading phase), on exercise day and for 8 consecutive days following a single bout of intense exercise (300 eccentric contractions at 30 deg/sec in an isokinetic dynamometer). In both conditions, blood samples and muscle biopsies will be collected at baseline, before the exercise protocol and at 2- and 8-days post-exercise. Muscle performance and soreness will also be assessed at the same time points. Before each trial, participants' dietary intake will be analyzed via diet recalls. Physical activity will be analyzed only at baseline via accelerometry. A 4-week washout period will be implemented between trials. Blood samples will be analyzed for inflammation and oxidative stress markers. Muscle samples will be analyzed for satellite cell responses and myogenic potential, protein levels of intracellular signaling proteins, muscle thiols and antioxidant enzyme activity.

Inclusion Criteria:

1. No recent history of musculoskeletal injury
2. Non-smokers.
3. Abstain from any vigorous physical activity during the study
4. Abstain from consumption of caffeine, alcohol, performance-enhancing or antioxidant supplements, NSAIDs and medications before (at least 6 months) and during the study.

Exclusion Criteria:

1. A known NAC intolerance or allergy
2. A recent febrile illness
3. A recent history of muscle lesion and/or lower limb trauma
4. Presence of metabolic diseases
5. Use of anti-inflammatory medication.
6. Use of medication interacting with muscle metabolism.