Reactive oxygen species and skeletal muscle adaptation to exercise
Physical exercise promotes signalling responses in skeletal muscle leading to alterations in protein synthesis and muscle phenotype. For example, as few as five consecutive days of endurance exercise (i.e. 60 min day−1
at 60% of maximal oxygen uptake) promotes an increase in both mitochondrial enzymes and antioxidants in the active skeletal muscles (Vincent et al.
2000). The fact that ROS are generated in contracting muscles and many signalling pathways are redox sensitive has raised the question of whether contraction-induced ROS production plays an essential role in skeletal muscle adaptation to aerobic exercise training. The short answer to this question is yes, and evidence to support this position follows.
Davies and colleagues provided the first suggestion that ROS production is a stimulus for skeletal muscle adaptation to exercise training (Davies et al.
1982). Since this initial proposal, many studies have supported this concept. For example, abundant in vitro
studies have demonstrated that exposure of cultured myotubes to oxidants (e.g. hydrogen peroxide) promotes the expression of numerous genes (Li et al.
2003; McArdle et al.
2004; Hansen et al.
2007; Irrcher et al.
2009; McClung et al.
2009). Specifically, hydrogen peroxide exposure has been shown to augment the expression of key antioxidant enzymes in myotubes (Franco et al.
1999). Moreover, a recent study reveals that exposure of myotubes to exogenous hydrogen peroxide increases peroxisome proliferator-activated receptor-γ coactivator-1 protein-α (PGC-1α) promoter activity and mRNA expression (Irrcher et al.
2009). Importantly, both effects were blocked when the antioxidant N
-acetylcysteine was added to the culture medium. It has also been reported that ROS production is a requirement for contraction-induced gene expression of PGC-1α in primary rat muscle cells (Silveira et al.
2006). Collectively, these in vitro
experiments demonstrate that ROS are capable of altering gene expression in cultured muscle cells.
Similar to the aforementioned cell culture studies, numerous reports support the concept that exercise-induced ROS production alters muscle gene expression and contributes to exercise-induced adaptations of skeletal muscle in vivo
. A common approach in many of these studies is to abolish the signalling effects of exercise-induced ROS production in skeletal muscle by treating animals or humans with antioxidants. For example, two independent reports have demonstrated that exercise-induced expression of heat shock protein 72 in rat skeletal and cardiac muscle is suppressed by antioxidant supplementation (Hamilton et al.
2003; Jackson et al.
2004). Also, two independent studies have recently concluded that antioxidant supplementation can retard important training adaptations in human skeletal muscle (Gomez-Cabrera et al.
2008; Ristow et al.
2009). Specifically, Gomez-Cabrera et al.
(2008) reported that oral administration of vitamin C in humans prevented exercise-induced expression of PGC-1α and mitochondrial biogenesis in skeletal muscle. Furthermore, vitamin C treatment also prevented exercise-induced expression of several antioxidant enzymes in muscle (Gomez-Cabrera et al.
2008). Similar results in humans have been reported by Ristow et al.
(2009). Together, these findings support the conclusion that ROS production plays an essential role in exercise-induced skeletal muscle adaptation.