Interaction between signalling pathways involved in skeletal muscle responses to endurance exercise

Abstract

The purpose of this review is to summarise the latest literature on the signalling pathways involved in transcriptional modulations of genes that encode contractile and metabolic proteins in response to endurance exercise. A special attention has been paid to the cooperation between signalling pathways and coordinated expression of protein families that establish myofibre phenotype. Calcium acts as a second messenger in skeletal muscle during exercise, conveying neuromuscular activity into changes in the transcription of specific genes. Three main calcium-triggered regulatory pathways acting through calcineurin, Ca(2+)-calmodulin-dependent protein kinases (CaMK) and Ca(2+)-dependent protein kinase C, transduce alterations in cytosolic calcium concentration to target genes. Calcineurin signalling, the most important of these Ca(2+)-dependent pathways, stimulates the activation of many slow-fibre gene expression, including genes encoding proteins involved in contractile process, Ca(2+) uptake and energy metabolism. It involves the interaction between multiple transcription factors and the collaboration of other Ca(2+)-dependent CaMKs. Although members of mitogen-activated protein kinase (MAPK) pathways are activated during exercise, their integration into other signalling pathways remains largely unknown. The peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator-1alpha (PGC-1alpha) constitutes a pivotal factor of the circuitry which coordinates mitochondrial biogenesis and which couples to the expression of contractile and metabolic genes with prolonged exercise.

The Molecular Bases of Training Adaptation

“…Individuals have different genetic capacity to perform and adapt to aerobic or anaerobic exercise (Bouchard et al 2000) and muscle fibre composition is an important contributing factor to this process. Nevertheless, while the mechanisms that transduce the fibre-type specific effect of contractile activity are incompletely understood, numerous signalling proteins and genes have been implicated in exercise-induced adaptation (Hawley 2002;Glass 2005;Koulmann and Bigard 2006).…”

“…Conclusive mechanistic data linking the effect of CaMK activation to cellular adaptation is currently lacking but downstream effects may be mediated, at least in part, through histone deacetylase nuclear extrusion via calcium signalling (Figure 1.6;Chin 2005;Liu et al 2005). Prolonged, low-amplitude intra-cellular calcium transients increase calcineurin activity that dephosphorylates and activates transcriptional promoters to upregulate gene expression (Michel et al 2004;Koulmann and Bigard 2006). The principle substrate targets of calcineurin include the nuclear factor of activated T cells (NFAT) and myocyte enhancer factor 2 (MEF2) families of transcription factors .…”

Measurement and Physiological Relevance of the Maximal Lipid Oxidation Rate During Exercise (LIPOXmax)

“…An overlook at the rapidly expanding body of knowledge in the field of molecular biology of muscle shows that either LI, HI, RT or IT are able to improve muscular function and to be helpful for the correction of metabolic disturbances (Burgomaster et al 2008). It is however important to emphasize that RT and ET act on separate and antagonistic intracellular pathways (Koulmann & Bigard, 2006), hence they are independant tools that cannot be expected to provide equivalent effects on muscle cells.…”

“…At the cellular level (Koulmann & Bigard, 2006) endurance training induces a set of regulatory adaptations that improve mitochondrial function and protein synthesis and overall, the enzymes for both CHO and fat oxidation are increased. As a result of these cellular adaptations, exercise training improves whole body lipid metabolism and carbohydrate tolerance, thus consisting in a fully recognized tool for reducing both blood lipids and glucose (see below).…”

“…In a study on dieting postmenopausal women with a total energy expenditure of 700 kcal/wk, ie, 8 kcal.kg body weight -1 wk -1 with LI being at 45-50% if heart rate reserve (HRR) and HI at 70-75% (vigourous-intensity) of HRR (Nicklas et al, 2009) found that with a similar amount of total weight loss, lean mass is preserved with either moderate-or vigorous-intensity aerobic exercise performed during caloric restriction and concluded that FFM is equally preserved with LI and HI. Both resistance (RE) and endurance (EE) exercise are able to stimulate mixed skeletal muscle protein synthesis, but the phenotypes induced by RE (myofibrillar protein accretion) and EE (mitochondrial expression) training are different and this is probably due to differential stimulation of myofibrillar and mitochondrial protein synthesis (Koulmann et al, 2006;Wilkinson et al, 2008;Harber et al, 2009). A mechanism that may play a role in this protective effect of LI is glycogen sparing.…”