Analysis of global gene expression in skeletal muscle during recovery from endurance and damaging resistance exercise.

摘要

Introduction. In skeletal muscle, altered mRNA expression after exercise contributes to: (i) re-establishing muscle cell homeostasis (homeostatic recovery); and (ii) inducing adaptation. The major purpose of this thesis was to analyze global mRNA expression after a bout of endurance (END) and damaging resistance (RES) exercise. Methods. 29 healthy, young, sedentary males performed a bout of high-intensity cycling (∼75 min; END) or 300 maximal eccentric contractions (damaging RES). Muscle biopsies were taken from the vastus lateralis before, and at 3 h and 48 h after exercise. We examined global mRNA expression in four subjects per group by using cDNA microarrays, and confirmed the expression of 15 transcripts in the other subjects using real-time RT-PCR. We also examined the expression of five housekeeping genes commonly used in exercise physiology, as well as various aspects of the stress response. Results. The major finding was that 160 genes were differentially expressed after END exercise and 235 after damaging RES exercise. Of these genes, 54 were common to both exercise bouts. END exercise induced the expression of genes involved in metabolism, mitochondrial biogenesis, oxidative stress management and signaling, and electrolyte transport across membranes, as well as those involved in cell stress management, proteolysis, apoptosis, growth, differentiation, and transcriptional activation. Important amongst these was a group of regulatory proteins that may mediate the alterations in muscle metabolism during recovery from END exercise and in response to END training, as well as a robust metallothionein response that may manage oxidative stress in skeletal muscle. Damaging RES exercise altered the expression of genes involved in cell stress management, muscle growth and remodeling, cholesterol and lipid homeostasis, membrane transport, and apoptosis. Important amongst these was an SREBP-2-mediated transcriptional program that is likely involved in de novo membrane biosynthesis, and several potential mediators of muscle hypertrophy. Genes common to both exercise bouts largely consist of those involved in cell stress management. Both exercise bouts induced the expression of several of the "housekeeping" genes, and led to muscle damage, inflammation, oxidative stress and myonuclear apoptosis. Conclusions and significance. The major contribution from this thesis is that we have characterized the transcriptional response to END and damaging RES exercise in skeletal muscle at two key timepoints. Our results offer novel insight into the molecular and cellular mechanisms that mediate homeostatic recovery and adaptation.