Paradoxically, both contractile activity and prolonged periods of muscle disuse promote increased ROS production in skeletal muscle fibres. Importantly, ROS serve as signalling molecules in each of these conditions to influence biochemical pathways and gene expression. Specifically, many signalling molecules are manipulated by ROS, including redox-sensitive kinases, phosphatases and the transcription factor NF-κB. These redox-sensitive molecules act as downstream effectors of ROS and serve as critical signalling events leading to skeletal muscle remodelling in response to increased contractile activity (i.e. physical exercise) or during disuse (e.g. immobilization).
Although progress has been made in understanding the role of ROS as signalling molecules in muscle fibres, many unanswered questions remain. A fundamental query of great importance is ‘how does ROS production in skeletal muscle fibres promote anabolic responses in some conditions (e.g. exercise training), whereas in other states (e.g. disuse), cellular ROS production promotes catabolic signalling?’ Several potential explanations exist for this dichotomy, including differences in the oxidant species produced, divergence in the temporal pattern of ROS production (i.e. acute versus chronic ROS production), disparity in the levels of ROS produced and/or differences in the cellular locations of ROS production. Systematic and well-controlled studies are needed to address these important issues.
An on-going limitation in redox biology investigations is the problem of quantifying the levels of different ROS in live cells. Indeed, this restriction has delayed advancements in this field for several years. The creation of sensitive and reliable technique(s) to quantify the levels of ROS in cells or tissues would greatly accelerate progress in oxidative stress research.
Note that much of the evidence linking ROS signalling to muscle adaptation is based on transcriptional changes (i.e. increased or decreased mRNA) in the cell. Future studies should also investigate the role that ROS signalling plays in the rates of translation and in post-translational modifications of proteins.
Hopefully, the questions outlined in this review will stimulate muscle biologists to pursue research in the emerging field of redox signalling. Future technical advances in cell signalling will provide powerful tools for use in redox studies and will supply new opportunities for scientists to address the important questions outlined in this report. Clearly, the field of redox signalling in skeletal muscle is at an exciting stage.