Reactive oxygen species are signalling molecules for skeletal muscle adaptation

Abstract

Increased reactive oxygen species (ROS) production is crucial to the remodelling that occurs in skeletal muscle in response to both exercise training and prolonged periods of disuse. This review discusses the redox-sensitive signalling pathways that are responsible for this ROS-induced skeletal muscle adaptation. We begin with a discussion of the sites of ROS production in skeletal muscle fibres. This is followed by an overview of the putative redox-sensitive signalling pathways that promote skeletal muscle adaptation. Specifically, this discussion highlights redox-sensitive kinases, phosphatases and the transcription factor nuclear factor-B. We also discuss the evidence that connects redox signalling to skeletal muscle adaptation in response to increased muscular activity (i.e. exercise training) and during prolonged periods of muscular inactivity (i.e. immobilization). In an effort to stimulate further research, we conclude with a discussion of unanswered questions about redox signalling in skeletal muscle.

Figure 1

An illustration of the potential sources of reactive oxygen species (ROS) production in skeletal muscleNote that superoxide anions (O₂^•−) can be produced at several sites within muscle fibres, including NADPH oxidase, xanthine oxidase and mitochondria. Abbreviations: NO^•, nitric oxide; O₂^•−, superoxide anion; and ONOO⁻, peroxynitrate.

Figure 2

Illustration of the interaction of kinases and phosphatases in the regulation of transcription factors and subsequent protein synthesis in skeletal muscle

Figure 3

Reactive oxygen species are predicted to activate several proteolytic pathways, including calpains, caspase-3 and the proteasome system in skeletal muscle